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| Content Provider | Journal of Biological Chemistry (JBC) |
|---|---|
| Author | Yu, Fujun Zheng, Jianjian Mao, Yuqing Dong, Peihong Lu, Zhongqiu Li, Guojun Guo, Chuanyong Liu, Zhanju Fan, Xiaoming |
| Abstract | Effective control of hepatic stellate cell (HSC) activation and proliferation is critical to the treatment of liver fibrosis. Long non-coding RNAs have been shown to play a pivotal role in the regulation of cellular processes. It has been reported that growth arrest-specific transcript 5 (GAS5) acts as a crucial mediator in the control of cell proliferation and growth. However, little is known about the role and underlying mechanism of GAS5 in liver fibrosis. In this study, our results indicated that GAS5 expression was reduced in mouse, rat, and human fibrotic liver samples and in activated HSCs. Overexpression of GAS5 suppressed the activation of primary HSCs in vitro and alleviated the accumulation of collagen in fibrotic liver tissues in vivo. We identified GAS5 as a target of microRNA-222 (miR-222) and showed that miR-222 could inhibit the expression of GAS5. Interestingly, GAS5 could also repress miR-222 expression. A pulldown assay further validated that GAS5 could directly bind to miR-222. As a competing endogenous RNAs, GAS5 had no effect on primary miR-222 expression. In addition, GAS5 was mainly localized in the cytoplasm. Quantitative RT-PCR further demonstrated that the copy numbers of GAS5 per cell are higher than those of miR-222. GAS5 increased the level of p27 protein by functioning as a competing endogenous RNA for miR-222, thereby inhibiting the activation and proliferation of HSCs. Taken together, a new regulatory circuitry in liver fibrosis has been identified in which RNAs cross-talk by competing for shared microRNAs. Our findings may provide a new therapeutic strategy for liver fibrosis. |
| Related Links | http://www.jbc.org/content/290/47/28286.abstract |
| Ending Page | 28298 |
| Starting Page | 28286 |
| Page Count | 13 |
| File Format | HTM / HTML PDF |
| ISSN | 00219258 |
| Journal | Journal of Biological Chemistry (JBC) |
| Issue Number | 47 |
| Volume Number | 290 |
| DOI | 10.1074/jbc.M115.683813 |
| e-ISSN | 1083351X |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2015-11-20 |
| Access Restriction | Open |
| Subject Keyword | Fibrosis Hepatic stellate cell (HSC) Long non-coding RNA (long ncRNA, lncRNA) MicroRNA (miRNA) RNA interference (RNAi) Competing endogenous RNA Growth arrest-specific transcript 5 Liver fibrosis MicroRNA-222 RNA |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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