The long non-coding RNA MALAT1 promotes the migration and invasion of hepatocellular carcinoma by sponging miR-204 and releasing SIRT1
| Autor: | Shuhui Tao, Le-Du Zhou, Jiebin Zhou, Zhouhua Hou, Xu-wen Xu, Xiaoyu Fu, Shui-ping Liu, Deming Tan |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Carcinoma Hepatocellular Immunoprecipitation Apoptosis 03 medical and health sciences 0302 clinical medicine Sirtuin 1 Cell Movement medicine Humans Neoplasm Invasiveness RC254-282 Cell Proliferation MALAT1 biology Liver Neoplasms Neoplasms. Tumors. Oncology. Including cancer and carcinogens RNA General Medicine Hep G2 Cells medicine.disease digestive system diseases Long non-coding RNA Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis Hepatocellular carcinoma Cancer research biology.protein Disease Progression Adenocarcinoma Female RNA Long Noncoding Cancer development |
| Zdroj: | Tumor Biology, Vol 39 (2017) |
| ISSN: | 1423-0380 |
| Popis: | Increasing evidence supports the significance of long non-coding RNA in cancer development. Several recent studies suggest the oncogenic activity of long non-coding RNA metastasis–associated lung adenocarcinoma transcript 1 (MALAT1) in hepatocellular carcinoma. In this study, we explored the molecular mechanisms by which MALAT1 modulates hepatocellular carcinoma biological behaviors. We found that microRNA-204 was significantly downregulated in sh-MALAT1 HepG2 cell and 15 hepatocellular carcinoma tissues by quantitative real-time polymerase chain reaction analysis. Through bioinformatic screening, luciferase reporter assay, RNA-binding protein immunoprecipitation, and RNA pull-down assay, we identified microRNA-204 as a potential interacting partner for MALAT1. Functionally, wound-healing and transwell assays revealed that microRNA-204 significantly inhibited the migration and invasion of hepatocellular carcinoma cells. Notably, sirtuin 1 was recognized as a direct downstream target of microRNA-204 in HepG2 cells. Moreover, si-SIRT1 significantly inhibited cell invasion and migration process. These data elucidated, by sponging and competitive binding to microRNA-204, MALAT1 releases the suppression on sirtuin 1, which in turn promotes hepatocellular carcinoma migration and invasion. This study reveals a novel mechanism by which MALAT1 stimulates hepatocellular carcinoma progression and justifies targeting metastasis–associated lung adenocarcinoma transcript 1 as a potential therapy for hepatocellular carcinoma. |
| Databáze: | OpenAIRE |
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