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Source: Oncotarget

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Total 624 results found since Jan 2013.

Long non-coding RNA HOTAIR promotes glioblastoma cell cycle progression in an EZH2 dependent manner.
In conclusion, HOTAIR promotes cell cycle progression in glioma as a result of the binding of its 5' domain to the PRC2 complex. PMID: 25428914 [PubMed - as supplied by publisher]
Source: Oncotarget - November 30, 2014 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Ret finger protein-like 3 promotes tumor cell growth by activating telomerase reverse transcriptase expression in human lung cancer cells.
In this study, we identified ret finger protein-like 3 (RFPL3) as a hTERT promoter binding protein in lung cancer cells. The high hTERT promoter-binding activity of RFPL3 was detected in lung cancer cells compared to normal cells. Chromatin immunoprecipitation confirmed RFPL3 as a tumor-specific hTERT promoter binding protein. Overexpression of RFPL3 activated hTERT promoter and up-regulated hTERT expression and telomerase activity. Inhibition of RFPL3 expression by siRNA suppressed hTERT promoter activation and telomerase activity. Inhibition of RFPL3 by siRNA or shRNA also significantly inhibited tumor cell growth in vit...
Source: Oncotarget - December 12, 2014 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Selective inhibition of histone deacetylase 2 induces p53-dependent survivin downregulation through MDM2 proteasomal degradation.
Authors: Seo SK, Hwang CS, Choe TB, Hong SI, Yi JY, Hwang SG, Lee HG, Oh ST, Lee YH, Park IC Abstract In the present study, we found that selective inhibition of histone deacetylase 2 (HDAC2) with small inhibitory RNA (siRNA) induced survivin downregulation in a p53-dependent manner. Interestingly, suberoylanilide hydroxamic acid (SAHA) or knockdown of HDAC2 induced downregulation of Mdm2, a negative regulator of p53, at the protein level. SAHA and/or HDAC2 siRNA increased Mdm2 ubiquitination, and MG132, an inhibitor of proteosome function, prevented HDAC2 inhibition-induced degradation of Mdm2. Clinically, the mRN...
Source: Oncotarget - January 27, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Cyclosporine A and tacrolimus inhibit bladder cancer growth through down-regulation of NFATc1.
In this study, we assessed biological significance of NFAT in human bladder cancer. Immunohistochemistry detected nuclear/cytoplasmic NFATc1 signals in 14 (21.5%)/34 (52.3%), respectively, of 65 muscle-invasive bladder carcinomas and showed that patients with nuclear NFATc1-positive tumor had a significantly higher risk of disease progression (P = 0.006). In bladder cancer cell lines, cyclosporine A (CsA) and tacrolimus (FK506), immunosuppressant drugs/non-selective NFAT inhibitors, attenuated NFATc1 expression and its nuclear translocation, NFAT transcriptional activity, and the expression of cyclooxygenase-2 and c-myc, d...
Source: Oncotarget - February 6, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Inhibition of ERK1/2 down-regulates the Hippo/YAP signaling pathway in human NSCLC cells.
Authors: You B, Yang YL, Xu Z, Dai Y, Liu S, Mao JH, Tetsu O, Li H, Jablons DM, You L Abstract Alterations of the EGFR/ERK and Hippo/YAP pathway have been found in non-small cell lung cancer (NSCLC). Herein, we show that ERK1 and ERK2 have an effect on the Hippo/YAP pathway in human NSCLC cells. Firstly, inhibition of ERK1/2 by siRNA or small-molecular inhibitors decreased the YAP protein level, the reporter activity of the Hippo pathway, and the mRNA levels of the Hippo downstream genes, CTGF, Gli2, and BIRC5. Secondly, degradation of YAP protein was accelerated after ERK1/2 depletion in NSCLC cell lines, in which...
Source: Oncotarget - March 5, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Ku80 cooperates with CBP to promote COX-2 expression and tumor growth.
Authors: Xiao Y, Wang J, Qin Y, Xuan Y, Jia Y, Hu W, Yu W, Dai M, Li Z, Yi C, Zhao S, Li M, Du S, Cheng W, Xiao X, Chen Y, Wu T, Meng S, Yuan Y, Liu Q, Huang W, Guo W, Wang S, Deng W Abstract Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku...
Source: Oncotarget - March 24, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

E2F1 enhances glycolysis through suppressing Sirt6 transcription in cancer cells.
Authors: Wu M, Seto E, Zhang J Abstract The fast proliferation of cancer cells requires reprogramming of its energy metabolism with aerobic glycolysis as a major energy source. Sirt6, a class III histone deacetylase, has been shown to down regulate glycolysis by inhibiting the expression of several key glycolytic genes. Based on the published study on the metabolic phenotype of E2F1 -/- mice and SIRT6 -/- mice, we hypothesize that E2F1 enhances glycolysis and inhibits the expression of Sirt6. Indeed, over-expressing of E2F1, but not its DNA binding deficient mutant, significantly enhanced glucose uptake and lactate...
Source: Oncotarget - April 1, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Inhibition of histamine receptor 3 suppresses glioblastoma tumor growth, invasion, and epithelial-to-mesenchymal transition.
In conclusion, overexpression of H3R is associated with glioma progression. Inhibition of H3R leads to suppressed invasion and EMT of GBM by inactivating the PI3K/Akt and MEK/ERK pathways in gliomas. PMID: 25940798 [PubMed - as supplied by publisher]
Source: Oncotarget - May 6, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients.
CONCLUSIONS: The combination of siG12D-LODER™ and chemotherapy is well tolerated, safe and demonstrated a potential efficacy in patients with LAPC. NCT01188785. PMID: 26009994 [PubMed - as supplied by publisher]
Source: Oncotarget - May 28, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

PP2A inhibitors arrest G2/M transition through JNK/Sp1- dependent down-regulation of CDK1 and autophagy-dependent up-regulation of p21.
Authors: Gong FR, Wu MY, Shen M, Zhi Q, Xu ZK, Wang R, Wang WJ, Zong Y, Li ZL, Wu Y, Zhou BP, Chen K, Tao M, Li W Abstract Protein phosphatase 2A (PP2A) plays an important role in the control of the cell cycle. We previously reported that the PP2A inhibitors, cantharidin and okadaic acid (OA), efficiently repressed the growth of cancer cells. In the present study, we found that PP2A inhibitors arrested the cell cycle at the G2 phase through a mechanism that was dependent on the JNK pathway. Microarrays further showed that PP2A inhibitors induced expression changes in multiple genes that participate in cell cycle tr...
Source: Oncotarget - June 9, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Focal adhesion kinase overexpression and its impact on human osteosarcoma.
Authors: Ren K, Lu X, Yao N, Chen Y, Yang A, Chen H, Zhang J, Wu S, Shi X, Wang C, Sun X Abstract Focal adhesion kinase (FAK) has been implicated in tumorigenesis in various malignancies. We sought to examine the expression patterns of FAK and the activated form, phosphorylated FAK (pFAK), in human osteosarcoma and to investigate the correlation of FAK expression with clinicopathologic parameters and prognosis. In addition, the functional consequence of manipulating the FAK protein level was investigated in human osteosarcoma cell lines. Immunohistochemical staining was used to detect FAK and pFAK in pathologic arc...
Source: Oncotarget - September 26, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Suppression of BRD4 inhibits human hepatocellular carcinoma by repressing MYC and enhancing BIM expression.
In this study, we investigated whether BRD4 could be a target for treatment of human hepatocellular carcinoma (HCC). We show that BRD4 is over-expressed in HCC tissues. Suppression of BRD4, either by siRNA or using JQ1, a pharmaceutical BRD4 inhibitor, reduced cell growth and induced apoptosis in HCC cell lines while also slowing HCC xenograft tumor growth in mice. JQ1 treatment induced G1 cell cycle arrest by repressing MYC expression, which led to the up-regulation of CDKN1B (P27). JQ1 also de-repressed expression of the pro-apoptotic BCL2L11 (BIM). Moreover, siRNA knockdown of BIM attenuated JQ1-triggered apoptosis in H...
Source: Oncotarget - November 19, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Integrative omics reveals MYCN as a global suppressor of cellular signalling and enables network-based therapeutic target discovery in neuroblastoma.
Authors: Duffy DJ, Krstic A, Halasz M, Schwarzl T, Fey D, Iljin K, Mehta JP, Killick K, Whilde J, Turriziani B, Haapa-Paananen S, Fey V, Fischer M, Westermann F, Henrich KO, Bannert S, Higgins DG, Kolch W Abstract Despite intensive study, many mysteries remain about the MYCN oncogene's functions. Here we focus on MYCN's role in neuroblastoma, the most common extracranial childhood cancer. MYCN gene amplification occurs in 20% of cases, but other recurrent somatic mutations are rare. This scarcity of tractable targets has hampered efforts to develop new therapeutic options. We employed a multi-level omics approach t...
Source: Oncotarget - December 20, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

The long noncoding RNA MALAT1 promotes tumor-driven angiogenesis by up-regulating pro-angiogenic gene expression.
Authors: Tee AE, Liu B, Song R, Li J, Pasquier E, Cheung BB, Jiang C, Marshall GM, Haber M, Norris MD, Fletcher JI, Dinger ME, Liu T Abstract Neuroblastoma is the most common solid tumor during early childhood. One of the key features of neuroblastoma is extensive tumor-driven angiogenesis due to hypoxia. However, the mechanism through which neuroblastoma cells drive angiogenesis is poorly understood. Here we show that the long noncoding RNA MALAT1 was upregulated in human neuroblastoma cell lines under hypoxic conditions. Conditioned media from neuroblastoma cells transfected with small interfering RNAs (siRNA) ta...
Source: Oncotarget - February 9, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Effective growth-suppressive activity of maternal embryonic leucine-zipper kinase (MELK) inhibitor against small cell lung cancer.
Authors: Inoue H, Kato T, Olugbile S, Tamura K, Chung S, Miyamoto T, Matsuo Y, Salgia R, Nakamura Y, Park JH Abstract Maternal embryonic leucine zipper kinase (MELK), that plays a critical role in maintenance of cancer stem cells (CSCs), is predominantly expressed in various types of human cancer including small cell lung cancer (SCLC). SCLC usually acquires resistance to anti-cancer drugs and portends dismal prognosis. We have delineated roles of MELK in development/progression of SCLC and examined anti-tumor efficacy of OTS167, a highly potent MELK inhibitor, against SCLC. MELK expression was highly upregulated i...
Source: Oncotarget - February 13, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research