MALAT1 functions as a competing endogenous RNA to mediate Rac1 expression by sequestering miR-101b in liver fibrosis

Emerging evidence shows that Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a pivotal role in cell proliferation, migration, and invasion in tumors. However, the biological role and underlying mechanism of MALAT1 in liver fibrosis remains undefined. In this study, up-regulatio...

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Published in:Cell cycle (Georgetown, Tex.) Tex.), 2015-01, Vol.14 (24), p.3885-3896
Main Authors: Yu, Fujun, Lu, Zhongqiu, Cai, Jing, Huang, Kate, Chen, Bicheng, Li, Guojun, Dong, Peihong, Zheng, Jianjian
Format: Article
Language:English
Subjects:
Animals
Cell Cycle - genetics
Cell Cycle - physiology
Cell Proliferation - genetics
Cell Proliferation - physiology
Hepatic Stellate Cells - metabolism
Liver Cirrhosis - genetics
Liver Cirrhosis - metabolism
Male
Mice
Mice, Inbred C57BL
MicroRNAs - genetics
rac1 GTP-Binding Protein - genetics
rac1 GTP-Binding Protein - metabolism
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
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Summary:Emerging evidence shows that Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a pivotal role in cell proliferation, migration, and invasion in tumors. However, the biological role and underlying mechanism of MALAT1 in liver fibrosis remains undefined. In this study, up-regulation of MALAT1 was observed in fibrotic liver tissues and in activated hepatic stellate cells (HSCs). In addition, depletion of MALAT1 inhibited the activation of HSCs in vitro and attenuated collagen deposits in vivo. Our results demonstrated that MALAT1 expression is negatively correlated with microRNA-101b (miR-101b) expression. Furthermore, there was a negative feedback loop between the levels of MALAT1 and miR-101b. Luciferase reporter assay indicated that MALAT1 and RAS-related C3 botulinum substrate 1 (Rac1) are targets of miR-101b. We uncovered that MALAT1 regulates Rac1 expression through miR-101b as a competing endogenous RNA (ceRNA), thereby influencing the proliferation, cell cycle and activation of primary HSCs. Collectively, The ceRNA regulatory network may prompt a better understanding of liver fibrogenesis and contribute to a novel therapeutic strategy for liver fibrosis.
ISSN:1538-4101
1551-4005
DOI:10.1080/15384101.2015.1120917