Dataset Information

HIF-1-miR-219-SMC4 Regulatory Pathway Promoting Proliferation and Migration of HCC under Hypoxic Condition.

ABSTRACT: This paper aims to investigate the function of structural maintenance of chromosome 4 (SMC4) in the progression of hepatocellular carcinoma (HCC) under hypoxic condition. In this study, we found that suppression of SMC4 could inhibit proliferation and migration of HCC cells through inducing G1 phase arrest and affecting process of epithelial-mesenchymal transition (EMT) under hypoxic condition. Moreover, we demonstrated that SMC4 was transcriptionally regulated by hypoxia-inducible factor-1 (HIF-1) under hypoxic condition. As SMC has been shown to be a target gene of miR-219, we observed that miR-219 was downregulated under hypoxic condition and suppression of HIF-1a could lead to the upregulation of miR-219. We also proved that miR-219 could affect the proliferation and migration of HCC cells under hypoxic condition. In conclusion, our study demonstrated a novel HIF-1-miR-219-SMC4 regulatory pathway under hypoxic condition in HCC cells.

SUBMITTER: Chen Y

PROVIDER: S-EPMC6885181 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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HIF-1-miR-219-SMC4 Regulatory Pathway Promoting Proliferation and Migration of HCC under Hypoxic Condition.

Chen Yang Y Huang Fei F Deng Liang L Yuan Xiaowei X Tao Qiang Q Wang Tielong T Li Dong D Fan Youwen Y Peng Quanzhou Q Tang Di D

BioMed research international 20191107

This paper aims to investigate the function of structural maintenance of chromosome 4 (SMC4) in the progression of hepatocellular carcinoma (HCC) under hypoxic condition. In this study, we found that suppression of SMC4 could inhibit proliferation and migration of HCC cells through inducing G1 phase arrest and affecting process of epithelial-mesenchymal transition (EMT) under hypoxic condition. Moreover, we demonstrated that SMC4 was transcriptionally regulated by hypoxia-inducible factor-1 (HIF ...[more]

PMID: 31828143

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Project description:BackgroundDrug resistance is a major contributing factor to chemotherapy failure in hepatocellular carcinoma (HCC) patients. However, the exact mechanism underlying the chemoresistance of HCC remains unknown.MethodsHepG2 cells were incubated with different concentrations of 5-fluorouracil (5-FU), and the Cell Counting Kit-8 assay was used to test the cell survival rate. The expression level of structural maintenance of chromosome 4 (SMC4) in drug-resistant cells was analyzed by real-time quantitative polymerase chain reaction (PCR) and western blotting. To assess autophagy, immunofluorescence was applied to detect the light chain 3 beta (LC3B) level in HepG2/5-FU cells. To further study the upstream regulation of miR (microRNA)-219/SMC4, a gene chip assay was performed. A luciferase reporter assay was used to determine whether long non-coding RNA-XIST (lncRNA-XIST) functions as a competitive endogenous RNA (ceRNA) for miR-219. Cellular proliferation was evaluated using MTT [3-(4,5)-dimethylthiahiazo (-z-y1)-2,5-di-phenytetrazoliumromide] and colony formation assays, wound healing and invasion assays were performed to study the invasion and migration ability of the cells, and flow cytometry assays were carried out to evaluate cell apoptosis.ResultsIn the present study, we established a drug-resistant hepatoma cell line named HepG2/5-FU. We confirmed that SMC4 may play an important role in hepatoma cell autophagy and could promote autophagy to increase the drug resistance of hepatoma cells. We also demonstrated that lncRNA-XIST may competitively bind to miR-219 by acting as a miRNA sponge, thereby preventing miR-219 from effectively reducing the expression of SMC4 and further affecting the autophagy and drug resistance of hepatoma cells via the adenosine 5'-monophosphate (AMP)-activated protein kinase/mechanistic target of rapamycin (AMPK/mTOR) pathway.ConclusionsOur study suggests that SMC4 may be a potential marker of a poor HCC response to chemotherapy and a novel therapeutic target for HCC chemotherapy.

Dataset Information

HIF-1-miR-219-SMC4 Regulatory Pathway Promoting Proliferation and Migration of HCC under Hypoxic Condition.

Publications

HIF-1-miR-219-SMC4 Regulatory Pathway Promoting Proliferation and Migration of HCC under Hypoxic Condition.

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