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Nrf2/ARE pathway activation is involved in negatively regulating heat-induced apoptosis in non-small cell lung cancer cells.
In this study, using immunocytochemistry and western blot analysis, we demonstrated that heat stress induced Nrf2/ARE activation through the nuclear translocation of Nrf2 in non-small cell lung cancer cells. Luciferase activity was also increased. Additionally, antioxidant enzymes were increased through Nrf2 activation after heat stress. Transfection of lung cancer cells with siRNA directed against Nrf2 increased heat cytotoxicity and cell apoptosis. Heat stress could induce reactive oxygen species (ROS) accumulation, while the antioxidant NAC obviously reduced cell apoptosis ratio, indicating that heat stress induced cell...
Source: Acta Biochimica et Biophysica Sinica - April 6, 2020 Category: Biochemistry Authors: Xie W, Tan B, Yang Z, Yu X, Chen L, Ran D, Xu Q, Zhou X Tags: Acta Biochim Biophys Sin (Shanghai) Source Type: research

YAP mediates the positive regulation of hnRNPK on the lung adenocarcinoma H1299 cell growth.
In this study, we observed that the expression pattern of hnRNPK in H1299 lung adenocarcinoma cells varied depending on the cell density in culture. Moreover, hnRNPK stimulated the ability of proliferation and colony formation of H1299 cells, which is important for the multilayered cell growth in culture. We further investigated whether there is an association between hnRNPK and the elements involved in the cell contact inhibition pathway. By using quantitative reverse transcriptase-polymerase chain reaction assay and a YAP activity reporter system, we found that hnRNPK upregulated the mRNA and protein levels and transcrip...
Source: Acta Biochimica et Biophysica Sinica - June 11, 2019 Category: Biochemistry Authors: Xu L, Zhang T, Huang W, Liu X, Lu J, Gao X, Zhang YF, Liu L Tags: Acta Biochim Biophys Sin (Shanghai) Source Type: research

The JAK/STAT Pathway in Skeletal Muscle Pathophysiology
Conclusion and Perspectives The IL-6/JAK/STAT signaling cascade plays a dominant role in skeletal muscle pathophysiology. IL-6 autocrine, paracrine, and endocrine functions assign to its downstream effectors pivotal importance in skeletal muscle-wasting-associated diseases and other multiple system diseases where muscle acts in communication with other organs. Targeting the components of the JAK/STAT pathway recently emerged as a strategic approach for the treatment of inflammatory diseases and human cancer. This review highlights the opposite outcomes on muscle biology caused by the amount of local and systemic release ...
Source: Frontiers in Physiology - April 29, 2019 Category: Physiology Source Type: research

Inhibition of SMYD2 Sensitized Cisplatin to Resistant Cells in NSCLC Through Activating p53 Pathway
In conclusion, the present study elucidated that the activity of SMYD2 in NSCLC may affect the cell sensitivity to chemotherapeutic agents, especially to CDDP. The elevated SMYD2 mediated CDDP resistance and malignant phenotype in NSCLC, indicating that SMYD2 may be a useful biomarker of CDDP resistance in NSCLC. Inhibition of SMYD2 contributes to the methylation-related activation of p53 and thus results in cell apoptosis. Furthermore, combination treatment with CDDP and an SMYD2 inhibitor had a synergistically antitumor effects in a xenograft model in vivo. Given that SMYD2 has reversible effects and is a targetable prot...
Source: Frontiers in Oncology - April 25, 2019 Category: Cancer & Oncology Source Type: research

An Ensemble Strategy to Predict Prognosis in Ovarian Cancer Based on Gene Modules
Conclusion Considering the heterogeneity and complexity of ovarian cancer, we demonstrated a new method to predict the prognosis of ovarian cancer based on the clustering information and gene co-expression network in each subtype of cancer patients. We divided the ovarian cancer data into three subtypes by clustering analysis and we found that the survival risks in these three subtypes were significantly different. We mined the important communities based on the co-expression networks in each subtype. There are 50, 73, and 92 communities in the first, second and third subtype, respectively. Next, we constructed a new ense...
Source: Frontiers in Genetics - April 23, 2019 Category: Genetics & Stem Cells Source Type: research

Endothelial Cell-Derived TGF- β Promotes Epithelial-Mesenchymal Transition via CD133 in HBx-Infected Hepatoma Cells
Conclusion: The study indicates that secretory factors like TGF-β from neighboring endothelial cells may enhance expression of CD133 and impart an aggressive EMT phenotype to HBx-infected hepatoma cells in HBV induced HCC. Introduction Hepatocellular Carcinoma (HCC) is one of the most common cancer worldwide, representing approximately 4% of all malignancies (1). It has been estimated that more than 50% of HCC cases in the world are associated with hepatitis B virus (HBV) (2). HBV is a partially double stranded DNA virus belonging to the Hepadnavirus family. The HBV genome is 3.2 kb in size and contains fou...
Source: Frontiers in Oncology - April 23, 2019 Category: Cancer & Oncology Source Type: research

Ability to Suppress TGF- β-Activated Myofibroblast Differentiation Distinguishes the Anti-pulmonary Fibrosis Efficacy of Two Danshen-Containing Chinese Herbal Medicine Prescriptions
Conclusion: This study suggests that a clinically efficacious cardiovascular Chinese herbal medicine (DLP) can be successfully repurposed to treat a lung disease in pulmonary fibrosis guided by TCM theory. Our comparative study between DLP and DHP demonstrated a critical requirement of suppressing both pro-inflammatory and pro-fibrotic pathways for the treatment of pulmonary fibrosis, supporting that a multi-component prescription capable of “removing both phlegm and blood stasis” will better achieve co-protection of heart and lung in PHD. Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic ...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Auranofin, an Anti-rheumatic Gold Drug, Aggravates the Radiation-Induced Acute Intestinal Injury in Mice
Conclusion In this study, we found that a non-toxic dose of auranofin significantly aggravated the severity of the radiation-induced intestinal injury. This suggests that auranofin treatment can be an independent factor that influences the risk of intestinal complications after pelvic or abdominal radiotherapy. Ethics Statement All the protocols used in this study were approved by the Institutional Animal Care and Use Committee of the Korean Institute of Radiological and Medical Sciences (IACUC permit number: KIRAMS217-0007). Author Contributions H-JL, JS, and Y-BL designed the experiments. EL and JK conducted the exp...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Sanguinarine Induces Apoptosis Pathway in Multiple Myeloma Cell Lines via Inhibition of the JaK2/STAT3 Signaling
In this study, we aimed to investigate the potential anti-proliferative and pro-apoptotic activities of SNG in a panel of MM cell lines (U266, IM9, MM1S, and RPMI-8226). SNG treatment of MM cells resulted in a dose-dependent decrease in cell viability through mitochondrial membrane potential loss and activation of caspase 3, 9, and cleavage of PARP. Pre-treatment of MM cells with a universal caspase inhibitor, Z-VAD-FMK, prevented SNG mediated loss of cell viability, apoptosis, and caspase activation, confirming that SNG-mediated apoptosis is caspase-dependent. The SNG-mediated apoptosis appears to be resulted from suppres...
Source: Frontiers in Oncology - April 16, 2019 Category: Cancer & Oncology Source Type: research

PGC1 β Regulates Breast Tumor Growth and Metastasis by SREBP1-Mediated HKDC1 Expression
Conclusions: PGC1β regulates breast cancer tumor growth and metastasis by SREBP1-mediated HKDC1 expression. This provides a novel therapeutic strategy through targeting the PGC1β/HKDC1 signaling pathway for breast cancer treatment. Introduction Breast cancer is a very common cancer with significant premature mortality in women. Around 12% of women in USA will have chance to be diagnosed with breast cancer during their lifetimes (1, 2). The development of breast cancer is regulated by many factors, and even as average survival rates have increased significantly as a result of many advanced treatments...
Source: Frontiers in Oncology - April 16, 2019 Category: Cancer & Oncology Source Type: research

Non-canonical Notch Signaling Regulates Actin Remodeling in Cell Migration by Activating PI3K/AKT/Cdc42 Pathway
In conclusion, our research results indicate that DAPT activates PI3K/AKT/Cdc42 signaling by non-canonical Notch pathway, and the activated Cdc42 promotes the filopodia formation and inhibits lamellipodia assembly, resulting in reduced migration of breast cancer cells. The results imply that non-canonical Notch signaling may play a very important role in the rapid response of cells to the extracellular signals. Author Contributions LG, JD, and LL designed the study and wrote and revised the manuscript. LL and LZ performed most of the experiments and data analysis. SZ, X-YZ, P-XM, Y-DM, Y-YW, YC, S-JT, and Y-JZ assisted i...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research

lncRNA ZEB1-AS1 Mediates Oxidative Low-Density Lipoprotein-Mediated Endothelial Cells Injury by Post-transcriptional Stabilization of NOD2
Conclusion We report the discovery that ZEB1-AS1 functionally participates in ox-LDL-induced ECs injury via LRPPRC-mediated stabilization of NOD2. Uncovering the precise role of ZEB1-AS1/LRPPRC/NOD2 pathway in the progression of ox-LDL-induced ECs death and AS will not only increase our knowledge of ox-LDL-induced AS, but also enable the development of novel therapeutic strategies to overcome oxidation product-induced diseases. Author Contributions XX and CL designed and mainly did the study. CM, ZD, and YD helped and did the study. Conflict of Interest Statement The authors declare that the research was conducted in ...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research

High Expression of DEPDC1 Promotes Malignant Phenotypes of Breast Cancer Cells and Predicts Poor Prognosis in Patients With Breast Cancer
In this study, the immunohistochemistry results demonstrated that DEPDC1 was high-expressed in breast cancer tissues compared with the paired adjacent normal breast tissues, and its tendency at protein level was consistent with mRNA level from TCGA data. Moreover, DEPDC1 mRNA level revealed the strongest association with poor prognosis and development in breast cancer. In vitro assays showed that DEPDC1 overexpression resulted in significant promotion of proliferation by regulating cell cycle in MCF-7 cells, whilst an opposite effect was found in the MDA-MB-231 cells with DEPDC1 deletion. Notably, further investigation ind...
Source: Frontiers in Oncology - April 11, 2019 Category: Cancer & Oncology Source Type: research

Hepatoma-Derived Growth Factor and DDX5 Promote Carcinogenesis and Progression of Endometrial Cancer by Activating β-Catenin
Conclusion: Our results provide novel evidence that HDGF interacts with DDX5 and promotes the progression of EC through the induction of β-catenin. Introduction Endometrial cancer (EC) comprises the most common malignancy involving the female genital tract and the fourth most common malignancy in women after breast, lung, and colorectal cancers (1). In 2012, approximately 320,000 new cases of EC were diagnosed worldwide and the incidence is increasing (2). Currently, endometrial carcinogenesis is thought to be a multi-step process involving the coordinated interaction of hormonal regulation, gene mutation, ad...
Source: Frontiers in Oncology - April 10, 2019 Category: Cancer & Oncology Source Type: research