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Circular RNA cMTO1 Promotes PTEN Expression Through Sponging miR-181b-5p in Liver Fibrosis
Hui Jin1, Chunxue Li2, Peihong Dong3
1Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Background:
Circular RNAs (circRNAs) are considered as key regulators of cancer biology. Recently, cMTO1 (a circRNA derived from MTO1 gene, hsa_circ_0007874) has been demonstrated to act as a tumor suppressor in hepatocellular carcinoma (HCC). However, the roles of cMTO1 in liver fibrosis are largely unknown.
Methods:
Expressions and roles of cMTO1 were examined in vivo and in vitro during liver fibrosis. The interaction between microRNA-181b-5p (miR-181b-5p) and cMTO1 was analyzed by luciferase activity assays and pull down assays.
Results:
cMTO1 was shown to be reduced in the liver from patients with cirrhosis. In addition, cMTO1 was down-regulated in the mouse fibrotic livers as well as activated hepatic stellate cells (HSCs). Restoring of cMTO1 led to a reduction in HSC proliferation. Results of immunofluorescence analysis showed that cMTO1 suppressed the expressions of α-SMA and type I collagen. cMTO1 was found to be expressed in the cytoplasm of HSCs. Further studies confirmed that cMTO1 and miR-181b-5p were co-located in the cytoplasm. Interestingly, there was an interaction between cMTO1 and miR-181b-5p. Results of luciferase reporter assays and pull down assays confirmed that miR-181b-5p could bind to cMTO1. cMTO1-inhibited HSC activation was blocked down by miR-181b-5p or PTEN. Meanwhile, PTEN was a target of miR-181b-5p.
Conclusion:
cMTO1 inhibits HSC activation, at least in part, through miR-181b-5p-mediated PTEN expression. Our results also suggest that cMTO1 may be a novel therapeutic target in liver fibrosis.
Insights
Circular RNA cMTO1 inhibits hepatic stellate cell activation and may be a therapeutic target for liver fibrosis. It functions by regulating microRNA-181b-5p and PTEN expression.
Area of Science:
- Molecular Biology
- Cell Biology
- Hepatology
Background:
- Circular RNAs (circRNAs) are key regulators in cancer biology.
- cMTO1 (hsa_circ_0007874) acts as a tumor suppressor in hepatocellular carcinoma (HCC).
- The role of cMTO1 in liver fibrosis remains largely unexplored.
Purpose of the Study:
- To investigate the expression and function of cMTO1 in liver fibrosis.
- To elucidate the molecular mechanism underlying cMTO1's role in hepatic stellate cell (HSC) activation.
- To assess cMTO1 as a potential therapeutic target for liver fibrosis.
Main Methods:
- In vivo and in vitro studies of cMTO1 expression and function during liver fibrosis.
- Luciferase activity and pull-down assays to analyze the interaction between cMTO1 and microRNA-181b-5p (miR-181b-5p).
- Immunofluorescence analysis to assess the impact of cMTO1 on fibrotic markers (α-SMA, type I collagen).
Main Results:
- cMTO1 expression was reduced in cirrhotic livers, fibrotic mouse livers, and activated HSCs.
- Restoring cMTO1 inhibited HSC proliferation and suppressed α-SMA and type I collagen expression.
- cMTO1 interacts with miR-181b-5p, which targets PTEN, and this interaction mediates cMTO1's inhibitory effect on HSC activation.
Conclusions:
- cMTO1 inhibits HSC activation, partly via miR-181b-5p-mediated PTEN expression.
- cMTO1 demonstrates potential as a novel therapeutic target for liver fibrosis.
- Further research into cMTO1's regulatory network in liver fibrosis is warranted.
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