title: MALAT1 functions as a competing endogenous RNA to mediate Rac1 expression by sequestering miR-101b in liver fibrosis.
abstract: 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.
authors.affiliation: a Department of Infectious Diseases ; The First Affiliated Hospital of Wenzhou Medical University ; Wenzhou , China.
authors.forename: Fujun
authors.initials: F
authors.lastname: Yu
authors.affiliation: b Department of Emergency ; The First Affiliated Hospital of Wenzhou Medical University ; Wenzhou , China.
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Lu
authors.affiliation: c Department of Gastroenterology ; Wenzhou central Hospital ; Wenzhou , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cai
authors.affiliation: d Department of Pathology ; The First Affiliated Hospital of Wenzhou Medical University ; Wenzhou , China.
authors.forename: Kate
authors.initials: K
authors.lastname: Huang
authors.affiliation: e Wenzhou Key Laboratory of Surgery; The First Affiliated Hospital of Wenzhou Medical University ; Wenzhou , China.
authors.forename: Bicheng
authors.initials: B
authors.lastname: Chen
authors.affiliation: f Department of Hepatology ; Ningbo Yinzhou Second Hospital ; Ningbo , China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
authors.affiliation: a Department of Infectious Diseases ; The First Affiliated Hospital of Wenzhou Medical University ; Wenzhou , China.
authors.forename: Peihong
authors.initials: P
authors.lastname: Dong
authors.affiliation: e Wenzhou Key Laboratory of Surgery; The First Affiliated Hospital of Wenzhou Medical University ; Wenzhou , China.
authors.forename: Jianjian
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D055166:Hepatic Stellate Cells / Q000378:metabolism; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C557041:MALAT1 long non-coding RNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D020830:rac1 GTP-Binding Protein
keywords: Competing endogenous RNA; Liver fibrosis; Long non-coding RNA; Metastasis-associated lung adenocarcinoma transcript 1; MicroRNA-101b