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MUC1-C drives myeloid leukaemogenesis and resistance to treatment by a survivin-mediated mechanism.
In this study, we demonstrate that MUC1-C overexpression is associated with increased leukaemia initiating capacity in an NSG mouse model. In concert with those results, MUC1-C silencing in multiple AML cell lines significantly reduced the establishment of AML in vivo. In addition, targeting MUC1-C with silencing or pharmacologic inhibition with GO-203 led to a decrease in active β-catenin levels and, in-turn, down-regulation of survivin, a critical mediator of leukaemia cell survival. Targeting MUC1-C was also associated with increased sensitivity of AML cells to Cytarabine (Ara-C) treatment by a survivin-dependent m...
Source: J Cell Mol Med - May 15, 2018 Category: Molecular Biology Authors: Stroopinsky D, Rajabi H, Nahas M, Rosenblatt J, Rahimian M, Pyzer A, Tagde A, Kharbanda A, Jain S, Kufe T, Leaf RK, Anastasiadou E, Bar-Natan M, Orr S, Coll MD, Palmer K, Ephraim A, Cole L, Washington A, Kufe D, Avigan D Tags: J Cell Mol Med Source Type: research

A novel human S10F-Hsp20 mutation induces lethal peripartum cardiomyopathy.
In this study, we investigated the functional significance of a novel human Hsp20 mutation (S10F) in peripartum cardiomyopathy. Previous findings showed that cardiac-specific overexpression of this mutant were associated with reduced autophagy, left ventricular dysfunction and early death in male mice. However, this study indicates that females have normal function with no alterations in autophagy but died within a week after 1-4 pregnancies. Further examination of mutant females revealed left ventricular chamber dilation and hypertrophic remodelling. Echocardiography demonstrated increases in left ventricular end-systolic...
Source: J Cell Mol Med - May 15, 2018 Category: Molecular Biology Authors: Liu GS, Gardner G, Adly G, Jiang M, Cai WF, Lam CK, Alogaili F, Robbins N, Rubinstein J, Kranias EG Tags: J Cell Mol Med Source Type: research

Chronic ethanol exposure of human pancreatic normal ductal epithelial cells induces cancer stem cell phenotype through SATB2.
Abstract The incidence of pancreatic cancer is on the rise. Risk factors for pancreatic cancer include alcohol toxicity and metabolic conditions such as obesity, hypertension, dyslipidaemia, insulin resistance and type 2 diabetes. However, the molecular mechanism by which chronic alcohol consumption contributes to pancreatic cancer is not well understood. The purpose of the study was to demonstrate the effects of long-term chronic ethanol exposure on the transformation of human pancreatic normal ductal epithelial (HPNE) cells. Our data showed that ethanol-transformed HPNE cells were more progressively transformed ...
Source: J Cell Mol Med - May 15, 2018 Category: Molecular Biology Authors: Yu W, Ma Y, Shankar S, Srivastava RK Tags: J Cell Mol Med Source Type: research

IRX5 promotes NF- κB signalling to increase proliferation, migration and invasion via OPN in tongue squamous cell carcinoma.
In this study, we observed that IRX5 was abnormally abundant in tongue squamous cell carcinoma (TSCC) tissues and cell lines. We used gain- and loss-of-function methods to overexpress and knockdown IRX5 expression in the TSCC cell line CAL27. Our results elucidated that elevated levels of IRX5 promoted proliferation, migration and invasion of TSCC cells, whereas stable or transient knockdown of IRX5 expression suppressed TSCC cell proliferation, migration and invasion. As a transcription factor, IRX5 performed this function by targeting osteopontin (OPN) promoter and activating the NF-κB pathway. Finally, studies in ...
Source: J Cell Mol Med - May 15, 2018 Category: Molecular Biology Authors: Huang L, Song F, Sun H, Zhang L, Huang C Tags: J Cell Mol Med Source Type: research

LncRNA HOXA11-AS promotes hepatocellular carcinoma progression by repressing miR-214-3p.
Abstract Accumulating studies supported that lncRNAs played important roles in tumorigenesis. LncRNA HOXA11-AS was a novel lncRNA that has been proved to involved in several tumours. However, the role of HOXA11-AS in the development of hepatocellular carcinoma (HCC) remains to be explained. In our study, we showed that HOXA11-AS expression was up-regulated in the HCC tissues, and the higher expression of HOXA11-AS was associated with the advanced stage in the HCC samples. In addition, we indicated that the expression of HOXA11-AS was up-regulated in HCC cell lines (Hep3B, SMMC-7721, MHCC97-H and BEL-7402) compared...
Source: J Cell Mol Med - May 15, 2018 Category: Molecular Biology Authors: Zhan M, He K, Xiao J, Liu F, Wang H, Xia Z, Duan X, Huang R, Li Y, He X, Yin H, Xiang G, Lu L Tags: J Cell Mol Med Source Type: research

Linc00483 as ceRNA regulates proliferation and apoptosis through activating MAPKs in gastric cancer.
In this study, we describe a novel functional lncRNA, linc00483, that is upregulated and associated with tumorigenesis, tumour size, metastasis and poor prognosis in gastric cancer. In our study, linc00483 promoted gastric cancer cell proliferation, invasiveness and metastasis in vitro and in vivo. Mechanistically, upregulated expression of linc00483 in gastric cancer acts as a sponge to absorb endogenous tumour suppressor miR-30a-3p. Furthermore, it restores SPAG9 expression, which is negatively regulated by miR-30a-3p, and actives MAPK signaling pathway in gastric cancer cells. Thus, linc00483 is an oncogenic l...
Source: J Cell Mol Med - May 15, 2018 Category: Molecular Biology Authors: Li D, Yang M, Liao A, Zeng B, Liu D, Yao Y, Hu G, Chen X, Feng Z, Du Y, Zhou Y, He J, Nie Y Tags: J Cell Mol Med Source Type: research

ZEB1-mediated vasculogenic mimicry formation associates with epithelial-mesenchymal transition and cancer stem cell phenotypes in prostate cancer.
Abstract The zinc finger E-box-binding homeobox 1 (ZEB1) induced the epithelial-mesenchymal transition (EMT) and altered ZEB1 expression could lead to aggressive and cancer stem cell (CSC) phenotypes in various cancers. Tissue specimens from 96 prostate cancer patients were collected for immunohistochemistry and CD34/periodic acid-Schiff double staining. Prostate cancer cells were subjected to ZEB1 knockdown or overexpression and assessment of the effects on vasculogenic mimicry formation in vitro and in vivo. The underlying molecular events of ZEB1-induced vasculogenic mimicry formation in prostate canc...
Source: J Cell Mol Med - May 12, 2018 Category: Molecular Biology Authors: Wang H, Huang B, Li BM, Cao KY, Mo CQ, Jiang SJ, Pan JC, Wang ZR, Lin HY, Wang DH, Qiu SP Tags: J Cell Mol Med Source Type: research

Mesenchymal stem cells promote lymphangiogenic properties of lymphatic endothelial cells.
Abstract Lymphatic metastasis is one of the main prognostic factors concerning long-term survival of cancer patients. In this regard, the molecular mechanisms of lymphangiogenesis are still rarely explored. Also, the interactions between stem cells and lymphatic endothelial cells (LEC) in humans have not been well examined. Therefore, the main objective of this study was to assess the interactions between mesenchymal stem cells (MSC) and LEC using in vitro angiogenesis assays. Juvenile LEC were stimulated with VEGF-C, bFGF, MSC-conditioned medium (MSC-CM) or by co-culture with MSC. LEC proliferation was asses...
Source: J Cell Mol Med - May 11, 2018 Category: Molecular Biology Authors: Robering JW, Weigand A, Pfuhlmann R, Horch RE, Beier JP, Boos AM Tags: J Cell Mol Med Source Type: research

Epithelial-mesenchymal transition softens head and neck cancer cells to facilitate migration in 3D environments.
Abstract The biological impact and signalling of epithelial-mesenchymal transition (EMT) during cancer metastasis has been established. However, the changes in biophysical properties of cancer cells undergoing EMT remain elusive. Here, we measured, via video particle tracking microrheology, the intracellular stiffness of head and neck cancer cell lines with distinct EMT phenotypes. We also examined cells migration and invasiveness in different extracellular matrix architectures and EMT-related signalling in these cell lines. Our results show that when cells were cultivated in three-dimensional (3D) environments, t...
Source: J Cell Mol Med - May 4, 2018 Category: Molecular Biology Authors: Chen YQ, Lan HY, Wu YC, Yang WH, Chiou A, Yang MH Tags: J Cell Mol Med Source Type: research

The miR-3127-5p/p-STAT3 axis up-regulates PD-L1 inducing chemoresistance in non-small-cell lung cancer.
In conclusion, microRNA-3127-5p induces PD-L1 elevation through regulating pSTAT3 expression. We also demonstrate that immune escape induced by PD-L1 can be dismissed by corresponding monoclonal antibody. PMID: 29726585 [PubMed - as supplied by publisher] (Source: J Cell Mol Med)
Source: J Cell Mol Med - May 4, 2018 Category: Molecular Biology Authors: Tang D, Zhao D, Wu Y, Yao R, Zhou L, Lu L, Gao W, Sun Y Tags: J Cell Mol Med Source Type: research

Metformin's antitumour and anti-angiogenic activities are mediated by skewing macrophage polarization.
Abstract Beneficial effects of metformin on cancer risk and mortality have been proved by epidemiological and clinical studies, thus attracting research interest in elucidating the underlying mechanisms. Recently, tumour-associated macrophages (TAMs) appeared to be implicated in metformin-induced antitumour activities. However, how metformin inhibits TAMs-induced tumour progression remains ill-defined. Here, we report that metformin-induced antitumour and anti-angiogenic activities were not or only partially contributed by its direct inhibition of functions of tumour and endothelial cells. By skewing TAM polarizat...
Source: J Cell Mol Med - May 4, 2018 Category: Molecular Biology Authors: Wang JC, Sun X, Ma Q, Fu GF, Cong LL, Zhang H, Fan DF, Feng J, Lu SY, Liu JL, Li GY, Liu PJ Tags: J Cell Mol Med Source Type: research

MiR-149 sensitizes esophageal cancer cell lines to cisplatin by targeting DNA polymerase β.
In conclusion, this study confirms that miR-149 may enhance the sensitivity of EC cell lines to cisplatin by targeting polβ, and that miR-149 may be unable to regulate the C1134G variant of polβ. Based on these findings, potential drugs could be developed with a focus on enhanced sensitivity of EC patients to chemotherapy. PMID: 29726631 [PubMed - as supplied by publisher] (Source: J Cell Mol Med)
Source: J Cell Mol Med - May 4, 2018 Category: Molecular Biology Authors: Wang Y, Chen J, Zhang M, Zhang W, Li M, Zang W, Dong Z, Zhao G Tags: J Cell Mol Med Source Type: research

The SHH/Gli axis regulates CD90-mediated liver cancer stem cell function by activating the IL6/JAK2 pathway.
This study aimed to investigate potential implications of SHH/Gli signalling in CD90+ liver cancer stem cells. Correlation of the expression of SHH signalling components and CD90 in liver cancer cells and clinical tissues, as well as in enriched CD90+ liver cancer stem cells and the TCGA database, were analysed by quantitative RT-PCR, Western blotting and flow cytometry. Functional analysis was conducted by siRNA-mediated CD90, Gli1 and Gli3 gene knockdown, SHH treatment and application of the JAK2 inhibitor AZD1480 and IL6 neutralizing antibody in CD90+ liver cancer stem cells, followed by cell proliferation, migration, s...
Source: J Cell Mol Med - May 2, 2018 Category: Molecular Biology Authors: Zhang K, Che S, Pan C, Su Z, Zheng S, Yang S, Zhang H, Li W, Wang W, Liu J Tags: J Cell Mol Med Source Type: research

Development of GMP-1 a molecular chaperone network modulator protecting mitochondrial function and its assessment in fly and mice models of Alzheimer's disease.
Abstract Mitochondrial dysfunction is an early feature of Alzheimer's disease (AD) and may play an important role in the pathogenesis of disease. It has been shown that amyloid beta peptide (Aβ) and amyloid precursor protein (APP) interact with mitochondria contributing to the mitochondrial dysfunction in AD. Prevention of abnormal protein targeting to mitochondria can protect normal mitochondrial function, increase neuronal survival and at the end, ameliorate symptoms of AD and other neurodegenerative disorders. First steps of mitochondrial protein import are coordinated by molecular chaperones Hsp70 and Hsp...
Source: J Cell Mol Med - April 27, 2018 Category: Molecular Biology Authors: Pavlov PF, Hutter-Paier B, Havas D, Windisch M, Winblad B Tags: J Cell Mol Med Source Type: research

A panel consisting of three novel circulating lncRNAs, is it a predictive tool for gastric cancer?
This study aimed to investigate the capacity of novel lncRNAs for diagnosing GC. A lncRNA microarray assay was used to screen differentially expressed lncRNAs between plasma of patients with GC and healthy controls. Plasma samples from 100 patients with healthy controls were used to construct a multiple-gene panel. An additional 50 pairs of GC patients with healthy controls were used to evaluate the diagnostic accuracy of the panel. Expression levels of lncRNAs were quantified through real-time polymerase chain reaction. The receiver operating characteristic curve and area under curve (AUC) were used to estimate the diagno...
Source: J Cell Mol Med - April 26, 2018 Category: Molecular Biology Authors: Liu J, Wang J, Song Y, Ma B, Luo J, Ni Z, Gao P, Sun J, Zhao J, Chen X, Wang Z Tags: J Cell Mol Med Source Type: research

Telocytes and interstitial cells of Cajal in the biliary system.
Abstract A novel type of interstitial tissue cells in the biliary tree termed telocytes (TCs), formerly known as interstitial Cajal-like cells (ICLCs), exhibits very particular features which unequivocally distinguish these cells from interstitial cells of Cajal (ICCs) and other interstitial cell types. Current research substantiates the existence of TCs and ICCs in the biliary system (gallbladder, extrahepatic bile duct, cystic duct, common bile duct and sphincter of Oddi). Here, we review the distribution, morphology and ultrastructure of TCs and ICCs in the biliary tree, with emphasis on their presumptive roles...
Source: J Cell Mol Med - April 26, 2018 Category: Molecular Biology Authors: Chen L, Yu B Tags: J Cell Mol Med Source Type: research

Glucocorticoids modulate multidrug resistance transporters in the first trimester human placenta.
Abstract The placental multidrug transporters, P-glycoprotein (P-gp, encoded by ABCB1) and breast cancer resistance protein (BCRP, ABCG2) protect the foetus from exposure to maternally derived glucocorticoids, toxins and xenobiotics. During pregnancy, maternal glucocorticoid levels can be elevated by stress or exogenous administration. We hypothesized that glucocorticoids modulate the expression of ABCB1/P-gp and ABCG2/BCRP in the first trimester human placenta. Our objective was to examine whether dexamethasone (DEX) or cortisol modulate first trimester placental expression of multidrug transporters and determine...
Source: J Cell Mol Med - April 24, 2018 Category: Molecular Biology Authors: Lye P, Bloise E, Nadeem L, Gibb W, Lye SJ, Matthews SG Tags: J Cell Mol Med Source Type: research

Up-regulation of miR-10b-3p promotes the progression of hepatocellular carcinoma cells via targeting CMTM5.
In this study, we investigated how miR-10b-3p regulated the proliferation, migration, invasion in hepatocellular carcinoma (HCC) at both in vitro and in vivo levels. CMTM5 was among the differentially expressed genes (data from TCGA). The expression of miR-10b-3p and CMTM5 was detected by qRT-PCR and Western blot (WB). TargetScan was used to acquire the binding sites. Dual-luciferase reporter gene assay was used to verify the direct target relationship between miR-10b-3p and CMTM5. WB analysis proved that miR-10b-3p suppressed CMTM5 expression. Furthermore, proliferation, invasion and migration of HCC cells were ...
Source: J Cell Mol Med - April 24, 2018 Category: Molecular Biology Authors: Guan L, Ji D, Liang N, Li S, Sun B Tags: J Cell Mol Med Source Type: research

Association of ATM and BMI-1 genetic variation with breast cancer risk in Han Chinese.
Abstract We tested the hypothesis that genetic variation in ATM and BMI-1 genes can alter the risk of breast cancer through genotyping 6 variants among 524 breast cancer cases and 518 cancer-free controls of Han nationality. This was an observational, hospital-based, case-control association study. Analyses of single variant, linkage, haplotype, interaction and nomogram were performed. Risk was expressed as odds ratio (OR) and 95% confidence interval (CI). All studied variants were in the Hardy-Weinberg equilibrium and were not linked. The mutant allele frequencies of rs1890637, rs3092856 and rs1801516 in ATM gene...
Source: J Cell Mol Med - April 24, 2018 Category: Molecular Biology Authors: Yue LL, Wang FC, Zhang ML, Liu D, Chen P, Mei QB, Li PH, Pan HM, Zheng LH Tags: J Cell Mol Med Source Type: research

Chemical, biochemical, preclinical and clinical studies of Ganoderma lucidum polysaccharide as an approved drug for treating myopathy and other diseases in China.
Abstract Ganoderma lucidum is an edible medicinal mushroom known as "Lingzhi" in China and "Reishi or Manetake" in Japan. It is a highly prized vitality-enhancing herb for more than 2000 years. G. lucidum polysaccharide (GLPS) has been identified as one of the major bioactive components and developed into a drug named "Ji 731 Injection" in China since 1973. The large-scale production of the drug began in 1985 and approved by the Chinese FDA as "Polysaccharidum of G. lucidum Karst Injection" (Ling Bao Duo Tang Zhu She Ye) in 2000, which is applied intramuscular...
Source: J Cell Mol Med - April 24, 2018 Category: Molecular Biology Authors: Zeng P, Guo Z, Zeng X, Hao C, Zhang Y, Zhang M, Liu Y, Li H, Li J, Zhang L Tags: J Cell Mol Med Source Type: research

Durable engraftment of genetically modified FVIII-secreting autologous bone marrow stromal cells in the intramedullary microenvironment.
Abstract Genetically modified FVIII-expressing autologous bone marrow-derived mesenchymal stromal cells (BMSCs) could cure haemophilia A. However, culture-expanded BMSCs engraft poorly in extramedullary sites. Here, we compared the intramedullary cavity, skeletal muscle, subcutaneous tissue and systemic circulation as tissue microenvironments that could support durable engraftment of FVIII-secreting BMSC in vivo. A zinc finger nuclease integrated human FVIII transgene into PPP1R12C (intron 1) of culture-expanded primary canine BMSCs. FVIII-secretory capacity of implanted BMSCs in each dog was expressed as an ...
Source: J Cell Mol Med - April 23, 2018 Category: Molecular Biology Authors: Lee SS, Sivalingam J, Nirmal AJ, Ng WH, Kee I, Song IC, Kiong CY, Gales KA, Chua F, Pena EM, Ogden BE, Kon OL Tags: J Cell Mol Med Source Type: research

A common regulatory variant in SLC35B4 influences the recurrence and survival of prostate cancer.
Abstract Single nucleotide polymorphisms (SNPs) within the regulatory elements of a gene can alter gene expression, making these SNPs of prime importance for candidate gene association studies. We aimed to determine whether such regulatory variants are associated with clinical outcomes in three cohorts of patients with prostate cancer. We used RegulomeDB to identify potential regulatory variants based on in silico predictions and reviewed genome-wide experimental findings. Overall, 131 putative regulatory SNPs with the highest confidence score on predicted functionality were investigated in two independent localiz...
Source: J Cell Mol Med - April 23, 2018 Category: Molecular Biology Authors: Huang EY, Chang YJ, Huang SP, Lin VC, Yu CC, Huang CY, Yin HL, Chang TY, Lu TL, Bao BY Tags: J Cell Mol Med Source Type: research

FKBP12.6 protects heart from AngII-induced hypertrophy through inhibiting Ca2+ /calmodulin-mediated signalling pathways in  vivo and in vitro.
In this study, we aimed to investigate the roles and mechanisms of FKBP12.6 in angiotensin II (AngII)-induced cardiac hypertrophy using various transgenic mouse models in vivo and in vitro. FKBP12.6 knockout (FKBP12.6-/- ) mice and cardiac-specific FKBP12.6 overexpressing (FKBP12.6 TG) mice were infused with AngII (1500 ng/kg/min) for 14 days subcutaneously by implantation of an osmotic mini-pump. The results showed that FKBP12.6 deficiency aggravated AngII-induced cardiac hypertrophy, while cardiac-specific overexpression of FKBP12.6 prevented hearts from the hypertrophic response to AngII stimulation ...
Source: J Cell Mol Med - April 22, 2018 Category: Molecular Biology Authors: Xiao YF, Zeng ZX, Guan XH, Wang LF, Wang CJ, Shi H, Shou W, Deng KY, Xin HB Tags: J Cell Mol Med Source Type: research

Limbal niche cells are a potent resource of adult mesenchymal progenitors.
Abstract Limbal niche cells located in the limbal Palisades of Vogt are mesenchymal stem cells that reside next to limbal basal epithelial cells. Limbal niche cells are progenitors that express embryonic stem cell markers such as Nanog, Nestin, Oct4, Rex1, Sox2 and SSEA4, mesenchymal cell markers such as CD73, CD90 and CD105, and angiogenesis markers such as Flk-1, CD31, CD34, VWF, PDGFRβ and α-SMA, but negative for CD45. In addition, the stemness of limbal niche cells can be maintained during their cell culture in a three-dimension environment. Furthermore, expanded limbal niche cells have the capabili...
Source: J Cell Mol Med - April 20, 2018 Category: Molecular Biology Authors: Guo P, Sun H, Zhang Y, Tighe S, Chen S, Su CW, Liu Y, Zhao H, Hu M, Zhu Y Tags: J Cell Mol Med Source Type: research

Endoplasmic reticulum stress induces spatial memory deficits by activating GSK-3.
Abstract Endoplasmic reticulum (ER) stress is involved in Alzheimer's disease (AD), but the mechanism is not fully understood. Here, we injected tunicamycin (TM), a recognized ER stress inducer, into the brain ventricle of Sprague-Dawley (SD) rats to induce the unfolded protein response (UPR), demonstrated by the enhanced phosphorylation of pancreatic ER kinase (PERK), inositol-requiring enzyme-1 (IRE-1) and activating transcription factor-6 (ATF-6). We observed that UPR induced spatial memory deficits and impairments of synaptic plasticity in the rats. After TM treatment, GSK-3β was activated and phosphoryla...
Source: J Cell Mol Med - April 19, 2018 Category: Molecular Biology Authors: Lin L, Cao J, Yang SS, Fu ZQ, Zeng P, Chu J, Ning LN, Zhang T, Shi Y, Tian Q, Zhou XW, Wang JZ Tags: J Cell Mol Med Source Type: research

Synthetic CpG oligonucleotides induce a genetic profile ameliorating murine myocardial I/R injury.
Abstract We previously demonstrated that pre-conditioning with CpG oligonucleotide (ODN) 1668 induces quick up-regulation of gene expression 3 hours post-murine myocardial ischaemia/reperfusion (I/R) injury, terminating inflammatory processes that sustain I/R injury. Now, performing comprehensive microarray and biocomputational analyses, we sought to further enlighten the "black box" beyond these first 3 hours. C57BL/6 mice were pretreated with either CpG 1668 or with control ODN 1612, respectively. Sixteen hours later, myocardial ischaemia was induced for 1 hour in a closed-chest model, f...
Source: J Cell Mol Med - April 19, 2018 Category: Molecular Biology Authors: Hilbert T, Markowski P, Frede S, Boehm O, Knuefermann P, Baumgarten G, Hoeft A, Klaschik S Tags: J Cell Mol Med Source Type: research

The TLR4-IRE1 α pathway activation contributes to palmitate-elicited lipotoxicity in hepatocytes.
The TLR4-IRE1α pathway activation contributes to palmitate-elicited lipotoxicity in hepatocytes. J Cell Mol Med. 2018 Apr 19;: Authors: Shen C, Ma W, Ding L, Li S, Dou X, Song Z Abstract Lipotoxicity induced by saturated fatty acids (SFAs) plays a pathological role in the development of non-alcoholic fatty liver disease (NAFLD); however, the exact mechanism(s) remain to be clearly elucidated. Toll-like receptor (TLR) 4 plays a fundamental role in activating the innate immune system. Intriguingly, hepatocytes express TLR4 and machinery for TLR4 signalling pathway. That liver-specific TLR4 knockou...
Source: J Cell Mol Med - April 19, 2018 Category: Molecular Biology Authors: Shen C, Ma W, Ding L, Li S, Dou X, Song Z Tags: J Cell Mol Med Source Type: research

MYCN is a novel oncogenic target in adult B-ALL that activates the Wnt/ β-catenin pathway by suppressing DKK3.
MYCN is a novel oncogenic target in adult B-ALL that activates the Wnt/β-catenin pathway by suppressing DKK3. J Cell Mol Med. 2018 Apr 19;: Authors: Kong D, Zhao L, Sun L, Fan S, Li H, Zhao Y, Guo Z, Lin L, Cui L, Wang K, Chen W, Zhang Y, Zhou J, Li Y Abstract Dickkopf-3 (DKK3) is frequently down-regulated by promoter hypermethylation and is closely associated with a poor prognosis in many cancers. Our previous studies have shown that miR-708 down-regulates DKK3 at the post-transcriptional level in B-ALL. However, whether transcriptional mechanisms lead to DKK3 silencing remains unclear. Here, we...
Source: J Cell Mol Med - April 19, 2018 Category: Molecular Biology Authors: Kong D, Zhao L, Sun L, Fan S, Li H, Zhao Y, Guo Z, Lin L, Cui L, Wang K, Chen W, Zhang Y, Zhou J, Li Y Tags: J Cell Mol Med Source Type: research

SUZ12 is a novel putative oncogene promoting tumorigenesis in head and neck squamous cell carcinoma.
Abstract The suppressor of zest 12 (SUZ12), one of the core polycomb repressive complex 2 (PRC2) components, has increasingly appreciated as a key mediator during human tumorigenesis. However, its expression pattern and oncogenic roles in head and neck squamous cell carcinoma (HNSCC) remain largely unexplored yet. Here, we sought to determine its expression pattern, clinicopathological significance and biological roles in HNSCC. Through data mining and interrogation from multiple publicly available databases, our bioinformatics analyses revealed that SUZ12 mRNA was significantly overexpressed in multiple HNSCC pat...
Source: J Cell Mol Med - April 18, 2018 Category: Molecular Biology Authors: Wu Y, Hu H, Zhang W, Li Z, Diao P, Wang D, Zhang W, Wang Y, Yang J, Cheng J Tags: J Cell Mol Med Source Type: research

TEAD4 exerts pro-metastatic effects and is negatively regulated by miR6839-3p in lung adenocarcinoma progression.
Abstract Several studies have shown the tumorigenesis role of transcriptional enhancer associate domain (TEAD) proteins; here, we initially explored expression, function and signalling mechanisms of TEAD4 in lung adenocarcinoma (LAD). Both the mRNA and protein levels of TEAD4 were increased in LAD tissues than those in adjacent nontumourous tissues. Besides, database search indicated a poorer clinical outcome in LAD patients with higher TEAD4 expression, revealing its potential tumour-promoting role. Therefore, we conducted cellular experiments to further investigate its effect on tumour phenotypes. Accordingly, T...
Source: J Cell Mol Med - April 18, 2018 Category: Molecular Biology Authors: Zhang Q, Fan H, Zou Q, Liu H, Wan B, Zhu S, Hu Y, Li H, Zhang C, Zhou L, Zhu Q, Xiao K, Zhang J, Zhan P, Lv T, Song Y Tags: J Cell Mol Med Source Type: research

Induced pluripotent stem cell-derived conditional medium promotes Leydig cell anti-apoptosis and proliferation via autophagy and Wnt/ β-catenin pathway.
In conclusion, iPS-CM could reduce H2 O2 -induced ILC apoptosis through the activation of autophagy, promote proliferation through up-regulation of Wnt/β-catenin pathway and enhance testosterone production through increasing steroidogenic enzyme expressions, which might be used in regenerative medicine for future. PMID: 29667777 [PubMed - as supplied by publisher] (Source: J Cell Mol Med)
Source: J Cell Mol Med - April 18, 2018 Category: Molecular Biology Authors: Guo X, Chen Y, Hong T, Chen X, Duan Y, Li C, Ge R Tags: J Cell Mol Med Source Type: research

PHAP1 promotes glioma cell proliferation by regulating the Akt/p27/stathmin pathway.
In conclusion, the above results suggest that PHAP1 expression is elevated in glioma patients, which may accelerate the proliferation of glioma cells by regulating the Akt/p27/stathmin pathway. PMID: 29667783 [PubMed - as supplied by publisher] (Source: J Cell Mol Med)
Source: J Cell Mol Med - April 18, 2018 Category: Molecular Biology Authors: Xie M, Ji Z, Bao Y, Zhu Y, Xu Y, Wang L, Gao S, Liu Z, Tian Z, Meng Q, Shi H, Yu R Tags: J Cell Mol Med Source Type: research

Up-regulated Cx43 phosphorylation at Ser368 prolongs QRS duration in myocarditis.
In this study, utilizing experimental autoimmune myocarditis (EAM) as a disease model, we show that the prolongation of QRS duration is accompanied by elevated phosphorylation of connexin 43 (Cx43) at Ser368 (pS368 Cx43). In cultured cells, inflammatory cytokine IL-1β activates p38 MAPK to up-regulate pS368 Cx43 and impairs cell-to-cell communication. In isolated hearts of normal rats, perfusion of IL-1β not only increases pS368 Cx43 but also impairs cell-to-cell communication and prolongs QRS duration. Furthermore, blockade of p38 MAPK down-regulates pS368 Cx43, improves cell-to-cell communication and reduces QR...
Source: J Cell Mol Med - April 17, 2018 Category: Molecular Biology Authors: Zhong C, Chang H, Wu Y, Zhou L, Wang Y, Wang M, Wu P, Qi Z, Zou J Tags: J Cell Mol Med Source Type: research

Oxidative stress in the pathogenesis of systemic scleroderma: An overview.
Abstract Systemic sclerosis (SSc) is a rare disorder of the connective tissue characterized by fibrosis of the skin, skeletal muscles and visceral organs. Additional manifestations include activation of the immune system and vascular injury. SSc causes disability and death as the result of end-stage organ failure. Two clinical subsets of the SSc are accepted: limited cutaneous SSc (lc-SSc) and diffuse cutaneous SSc (dc-SSc). At present, the aetiology and pathogenesis of SSc remain obscure, and consequently, disease outcome is unpredictable. Numerous studies suggest that reactive oxidizing species (ROS) play an imp...
Source: J Cell Mol Med - April 17, 2018 Category: Molecular Biology Authors: Vona R, Giovannetti A, Gambardella L, Malorni W, Pietraforte D, Straface E Tags: J Cell Mol Med Source Type: research

miR-1-3p and miR-206 sensitizes HGF-induced gefitinib-resistant human lung cancer cells through inhibition of c-Met signalling and EMT.
In this study, we showed that miR-1-3p and miR-206 restored the sensitivities of lung cancer cells PC-9 and HCC-827 to gefitinib in present of HGF. For the mechanisms, we demonstrated that both miR-1-3p and miR-206 directly target HGF receptor c-Met in lung cancer. Knockdown of c-Met mimicked the effects of miR-1-3p and miR-206 transfections Meanwhile, c-Met overexpression attenuated the effects of miR-1-3p and miR-206 in HGF-induced gefitinib resistance of lung cancers. Furthermore, we showed that miR-1-3p and miR-206 inhibited c-Met downstream Akt and Erk pathway and blocked HGF-induced epithelial-mesenchymal transition ...
Source: J Cell Mol Med - April 17, 2018 Category: Molecular Biology Authors: Jiao D, Chen J, Li Y, Tang X, Wang J, Xu W, Song J, Li Y, Tao H, Chen Q Tags: J Cell Mol Med Source Type: research

Microenvironment-induced PIM kinases promote CXCR4-triggered mTOR pathway required for chronic lymphocytic leukaemia cell migration.
on W, Gałęzowski M, Windak R, Brzózka K, Juszczyński P Abstract Lymph node microenvironment provides chronic lymphocytic leukaemia (CLL) cells with signals promoting their survival and granting resistance to chemotherapeutics. CLL cells overexpress PIM kinases, which regulate apoptosis, cell cycle and migration. We demonstrate that BCR crosslinking, CD40 stimulation, and coculture with stromal cells increases PIMs expression in CLL cells, indicating microenvironment-dependent PIMs regulation. PIM1 and PIM2 expression at diagnosis was higher in patients with advanced disease (Binet C vs. Binet A/B) and in...
Source: J Cell Mol Med - April 17, 2018 Category: Molecular Biology Authors: Białopiotrowicz E, Górniak P, Noyszewska-Kania M, Puła B, Makuch-Łasica H, Nowak G, Bluszcz A, Szydłowski M, Jabłonska E, Piechna K, Sewastianik T, Polak A, Lech-Marańda E, Budziszewska BK, Wasylecka-Juszczyńska M, Borg K, Warzocha K, Czardybon W, Tags: J Cell Mol Med Source Type: research

Hydrogen sulphide increases pulmonary veins and atrial arrhythmogenesis with activation of protein kinase C.
In conclusion, through protein kinase C signalling, H2 S increases PV and atrial arrhythmogenesis, which may contribute to air pollution-induced AF. PMID: 29659148 [PubMed - as supplied by publisher] (Source: J Cell Mol Med)
Source: J Cell Mol Med - April 16, 2018 Category: Molecular Biology Authors: Chan CS, Lin YK, Kao YH, Chen YC, Chen SA, Chen YJ Tags: J Cell Mol Med Source Type: research

Nrf2 attenuates inflammatory response in COPD/emphysema: Crosstalk with Wnt3a/ β-catenin and AMPK pathways.
In conclusion, Nrf2 mediates the protective effects of both Wnt3a/β-catenin and AMPK on lung inflammatory responses during the development of COPD/emphysema. These findings provide potential therapeutic targets for the intervention of COPD/emphysema. PMID: 29659176 [PubMed - as supplied by publisher] (Source: J Cell Mol Med)
Source: J Cell Mol Med - April 16, 2018 Category: Molecular Biology Authors: Cui W, Zhang Z, Zhang P, Qu J, Zheng C, Mo X, Zhou W, Xu L, Yao H, Gao J Tags: J Cell Mol Med Source Type: research

Common genetic variants in GAL, GAP43 and NRSN1 and interaction networks confer susceptibility to Hirschsprung disease.
Abstract Hirschsprung disease (HSCR) is a severe multifactorial genetic disorder. Microarray studies indicated GAL, GAP43 and NRSN1 might contribute to the altered risk in HSCR. Thus, we focused on genetic variations in GAL, GAP43 and NRSN1, and the gene-gene interactions involved in HSCR susceptibility. We recruited a strategy combining case-control study and MassArray system with interaction network analysis. For GAL, GAP43 and NRSN1, a total of 18 polymorphisms were assessed in 104 subjects with sporadic HSCR and 151 controls of Han Chinese origin. We found statistically significant differences between HSCR and...
Source: J Cell Mol Med - April 14, 2018 Category: Molecular Biology Authors: Wang Y, Yan W, Wang J, Zhou Y, Chen J, Gu B, Cai W Tags: J Cell Mol Med Source Type: research

Hepatoprotective effect of Herpetospermum caudigerum Wall. on carbon tetrachloride-induced hepatic fibrosis in rats.
This study was investigated to explore the protective effects of HCW on hepatic fibrosis and the possible mechanism in a rat model. Hepatic fibrosis was established by intragastric administration of 3 ml/kg carbon tetrachloride (CCl4 ) twice a week for 6 weeks. CCl4 -treated rats were received HCW (1 and 3 g/kg/d) and silymarin (0.1 g/kg/d) from 3 to 6 weeks. The results showed that HCW could significantly decrease the levels of AST, ALT, HA, LN, PCIII, Col IV, TNF-α, IL-1β and IL-6. Moreover, HCW could effectively inhibit collagen deposition and reduce the pathological damage. Analysis ...
Source: J Cell Mol Med - April 14, 2018 Category: Molecular Biology Authors: Feng X, Zhong GJ, Deng Ba DJ, Yang B, Chen L, Du S Tags: J Cell Mol Med Source Type: research

Human umbilical cord mesenchymal stem cells facilitate the up-regulation of miR-153-3p, whereby attenuating MGO-induced peritoneal fibrosis in rats.
In this study, we tried to profile whether miRNA expression differences exist after human umbilical cord mesenchymal stem cells (hUCMSCs) treatment in PF rats and investigate the possible role of miR-153-3p involved in anti-EMT process. We randomly assigned 34 rats into three groups: control group (Group Control), MGO-induced PF rats (Group MGO) and hUCMSCs-treated rats (Group MGO + hUCMSCs). MiRNA microarrays and real-time PCR analyses were conducted in three groups. α-SMA, Snail1 and E-cadherin expression were detected by Western blot. Luciferase reporter assays were used to detect the effects of miR-153-...
Source: J Cell Mol Med - April 14, 2018 Category: Molecular Biology Authors: Li D, Lu Z, Li X, Xu Z, Jiang J, Zheng Z, Jia J, Lin S, Yan T Tags: J Cell Mol Med Source Type: research

Stathmin inhibits proliferation and differentiation of dental pulp stem cells via sonic hedgehog/Gli.
This study aimed to identify the effect of Stathmin on the proliferation and osteogenic/odontoblastic differentiation of human dental pulp stem cells (hDPSCs) and to explore whether the Shh signalling pathway was involved in this regulation. First, Stathmin was expressed in the cytoplasm and on the cell membranes of hDPSCs by cell immunofluorescence. Then, by constructing a lentiviral vector, the expression of Stathmin in hDPSCs was inhibited. Treatment with Stathmin shRNA (shRNA-Stathmin group) inhibited the ability of hDPSCs to proliferate, as demonstrated by a CCK8 assay and flow cytometry analysis, and suppressed the o...
Source: J Cell Mol Med - April 14, 2018 Category: Molecular Biology Authors: Ma D, Yu H, Xu S, Wang H, Zhang X, Ning T, Wu B Tags: J Cell Mol Med Source Type: research

TP53INP1 inhibits hypoxia-induced vasculogenic mimicry formation via the ROS/snail signalling axis in breast cancer.
Abstract Tumour protein p53-inducible nuclear protein 1 (TP53INP1) is a tumour suppressor associated with malignant tumour metastasis. Vasculogenic mimicry (VM) is a new tumour vascular supply pattern that significantly influences tumour metastasis and contributes to a poor prognosis. However, the molecular mechanism of the relationship between TP53INP1 and breast cancer VM formation is unknown. Here, we explored the underlying mechanism by which TP53INP1 regulates VM formation in vitro and in vivo. High TP53INP1 expression was not only negatively correlated with a poor prognosis but also had a negative ...
Source: J Cell Mol Med - April 14, 2018 Category: Molecular Biology Authors: Wang Y, Sun H, Zhang D, Fan D, Zhang Y, Dong X, Liu S, Yang Z, Ni C, Li Y, Liu F, Zhao X Tags: J Cell Mol Med Source Type: research

Long noncoding RNA MALAT1 enhances the docetaxel resistance of prostate cancer cells via miR-145-5p-mediated regulation of AKAP12.
In this study, we firstly notified that the MALAT1 expression levels were up-regulated in clinical DTX-resistant PCa samples. Overexpressed MALAT1 promoted cell proliferation, migration and invasion but decreased cell apoptosis rate of PCa cells in spite of DTX treatment. We identified miR-145-5p as a target of MALAT1. MiR-145-5p overexpression in PC3-DTX led to inhibited cell proliferation, migration and invasion as well as reduced chemoresistance to DTX, which was attenuated by MALAT1. Moreover, we determined that AKAP12 was a target of miR-145-5p, which significantly induced chemoresistance of PCa cells to DTX. Besides,...
Source: J Cell Mol Med - April 6, 2018 Category: Molecular Biology Authors: Xue D, Lu H, Xu HY, Zhou CX, He XZ Tags: J Cell Mol Med Source Type: research

Elevated CRB3 expression suppresses breast cancer stemness by inhibiting β-catenin signalling to restore tamoxifen sensitivity.
Elevated CRB3 expression suppresses breast cancer stemness by inhibiting β-catenin signalling to restore tamoxifen sensitivity. J Cell Mol Med. 2018 Mar 30;: Authors: Li P, Feng C, Chen H, Jiang Y, Cao F, Liu J, Liu P Abstract Tamoxifen is a first-line drug for hormone therapy (HT) in oestrogen receptor-positive breast cancer patients. However, 20% to 30% of those patients are resistant to tamoxifen treatment. Cancer stem cells (CSCs) have been implicated as one of the mechanisms responsible for tamoxifen resistance. Our previous study indicated that decreased expression of the CRB3 gene confers ...
Source: J Cell Mol Med - March 30, 2018 Category: Molecular Biology Authors: Li P, Feng C, Chen H, Jiang Y, Cao F, Liu J, Liu P Tags: J Cell Mol Med Source Type: research

LncRNA NR2F1-AS1 regulates hepatocellular carcinoma oxaliplatin resistance by targeting ABCC1 via miR-363.
Abstract Emerging evidence has validated the vital role of long non-coding RNA (lncRNA) in the chemoresistance of cancer treatment. In the present study, we investigate the function of lncRNA NR2F1-AS1 on oxaliplatin (OXA) resistance of hepatocellular carcinoma (HCC) and discover the underlying molecular mechanism. Results revealed that lncRNA NR2F1-AS1 was up-regulated in oxaliplatin-resistant HCC tissue and cells using microarray analysis and RT-PCR. Meanwhile, ABCC1 protein was overexpressed in OXA-resistant HCC cells (Huh7/OXA and HepG2/OXA). In vitro, NR2F1-AS1 knockdown reduced the invasion, migration, drug-...
Source: J Cell Mol Med - March 30, 2018 Category: Molecular Biology Authors: Huang H, Chen J, Ding CM, Jin X, Jia ZM, Peng J Tags: J Cell Mol Med Source Type: research

Alterations of polyunsaturated fatty acid metabolism in ovarian tissues of polycystic ovary syndrome rats.
This study aimed to explore alterations in the levels of PUFAs and their metabolites in serum and ovarian tissues in a PCOS rat model treated with a high-fat diet and andronate. Levels of PUFAs and their metabolites were measured using gas/liquid chromatography-mass spectrometry after the establishment of a PCOS rat model. Only 3 kinds of PUFAs [linoleic acid, arachidonic acid (AA) and docosahexaenoic acid] were detected in both the circulation and ovarian tissues of the rats, and their concentrations were lower in ovarian tissues than in serum. Moreover, significant differences in the ovarian levels of AA were observed be...
Source: J Cell Mol Med - March 30, 2018 Category: Molecular Biology Authors: Huang R, Xue X, Li S, Wang Y, Sun Y, Liu W, Yin H, Tao T Tags: J Cell Mol Med Source Type: research

NEFA-induced ROS impaired insulin signalling through the JNK and p38MAPK pathways in non-alcoholic steatohepatitis.
Abstract The aim of this study was to investigate the changes in hepatic oxidative phosphorylation (OXPHOS) complexes (COs) in patients and cows with non-alcoholic steatohepatitis (NASH) and to investigate the mechanism that links mitochondrial dysfunction and hepatic insulin resistance induced by non-esterified fatty acids (NEFAs). Patients and cows with NASH displayed high blood NEFAs, TNF-α and IL-6 concentrations, mitochondrial dysfunction and insulin resistance. The protein levels of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), mitofusin-2 (Mfn-2) and OXPHOS co...
Source: J Cell Mol Med - March 30, 2018 Category: Molecular Biology Authors: Gao W, Du X, Lei L, Wang H, Zhang M, Wang Z, Li X, Liu G, Li X Tags: J Cell Mol Med Source Type: research

Inflammatory factor receptor Toll-like receptor 4 controls telomeres through heterochromatin protein 1 isoforms in liver cancer stem cell.
This study elucidates a novel protection mechanism of TLR4 in liver cancer stem cells and suggests that TLR4 can be used as a novel therapeutic target for liver cancer. PMID: 29602239 [PubMed - as supplied by publisher] (Source: J Cell Mol Med)
Source: J Cell Mol Med - March 30, 2018 Category: Molecular Biology Authors: Zheng Q, Xu J, Lin Z, Lu Y, Xin X, Li X, Yang Y, Meng Q, Wang C, Xiong W, Lu D Tags: J Cell Mol Med Source Type: research

The role of septin 7 in physiology and pathological disease: A systematic review of current status.
Abstract Septins are a conserved family of cytoskeletal GTPases present in different organisms, including yeast, drosophila, Caenorhabditis elegans and humans. In humans, septins are involved in various cellular processes, including exocytosis, apoptosis, leukemogenesis, carcinogenesis and neurodegeneration. Septin 7 is unique out of 13 human septins. Mammalian septin 6, septin 7, septin 2 and septin 9 coisolate together in complexes to form the core unit for the generation of the septin filaments. Physiological septin filaments are hetero-oligomeric complexes consisting of core septin hexamers and octamers. Furth...
Source: J Cell Mol Med - March 30, 2018 Category: Molecular Biology Authors: Wang X, Fei F, Qu J, Li C, Li Y, Zhang S Tags: J Cell Mol Med Source Type: research