PMID- 37919785 OWN - NLM STAT- MEDLINE DCOM- 20231106 LR - 20231119 IS - 1479-5876 (Electronic) IS - 1479-5876 (Linking) VI - 21 IP - 1 DP - 2023 Nov 2 TI - LncRNA-Gm9866 promotes liver fibrosis by activating TGFbeta/Smad signaling via targeting Fam98b. PG - 778 LID - 10.1186/s12967-023-04642-1 [doi] LID - 778 AB - OBJECTIVE: The exact mechanism and target molecules of liver fibrosis have remained largely elusive. Here, we investigated the role of long noncoding RNA Gm9866(lncRNA-Gm9866) on liver fibrosis. METHODS: The transcription of lncRNA-Gm9866 in activated cells and mouse fibrotic livers was determined by quantitative polymerase chain reaction (qRT-PCR). The effects of lentivirus-mediated knockdown or overexpression of lncRNA-Gm9866 in liver fibrosis were examined in vitro and in vivo. Furthermore, bioinformatics analysis, cell samples validation, fluorescence in situ hybridization (FISH) co-localization, RNA binding protein immunoprecipitation (RIP), actinomycin D test and Western blot (WB) were carried out to explore the potential mechanism of lncRNA-Gm9866. RESULTS: The expression of alpha-smooth muscle actin (alpha-SMA), Collagen I (COL-1) and lncRNA-Gm9866 were significantly increased in tissues and cells. Overexpressing lncRNA-Gm9866 promoted the activation of hepatic stellate cells (HSCs). Silencing lncRNA-Gm9866 inhibited the activation of HSCs and transforming growth factor-beta1 (TGFbeta1) induced fibrosis. Overexpressing lncRNA-Gm9866 promoted hepatocytes (HCs) apoptosis and the expression of pro-fibrogenic genes, inhibited the proliferation and migration of HCs. Knockdown of lncRNA-Gm9866 inhibited the apoptosis of HCs, the expression of pro-fibrogenic genes, TGFbeta1 induced fibrosis and the occurrence of carbon tetrachloride (CCl4)-induced liver fibrosis, and promoted the proliferation and migration of HCs. Mechanistically, lncRNA-Gm9866 may directly bine with Fam98b. Silencing Fam98b in stably overexpressing lncRNA-Gm9866 cell lines reversed the increase of pro-fibrogenic genes and pro-apoptotic genes, fibrosis related pathway protein TGFbeta1, Smad2/3, p-Smad2/3 and Notch3 induced by overexpressing lncRNA-Gm9866. CONCLUSIONS: LncRNA-Gm9866 may regulate TGFbeta/Smad and Notch pathways by targeting Fam98b to regulate liver fibrosis. LncRNA-Gm9866 may be a new target for diagnosis and treatment of liver fibrosis. CI - (c) 2023. The Author(s). FAU - Liao, Xiaomin AU - Liao X AD - Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, 530021, Guangxi, China. FAU - Ruan, Xianxian AU - Ruan X AD - Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, 530021, Guangxi, China. FAU - Yao, Peishan AU - Yao P AD - Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, 530021, Guangxi, China. FAU - Yang, Dan AU - Yang D AD - Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. FAU - Wu, Xianbin AU - Wu X AD - Department of Gastroenterology, The Wuming Affiliated Hospital of Guangxi Medical University, Nanning, 530000, Guangxi, China. FAU - Zhou, Xia AU - Zhou X AD - Department of Emergency, People's Hospital of Guizhou Province, Guiyang, 550000, Guizhou, China. FAU - Jing, Jie AU - Jing J AD - Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, 530021, Guangxi, China. FAU - Wei, Dafu AU - Wei D AD - Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, 530021, Guangxi, China. FAU - Liang, Yaodan AU - Liang Y AD - Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, 530021, Guangxi, China. FAU - Zhang, Taicheng AU - Zhang T AD - Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, 530021, Guangxi, China. FAU - Qin, Shanyu AU - Qin S AD - Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, 530021, Guangxi, China. qinshanyu@gxmu.edu.cn. FAU - Jiang, Haixing AU - Jiang H AUID- ORCID: 0000-0003-2974-2035 AD - Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, 530021, Guangxi, China. jianghaixing@gxmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231102 PL - England TA - J Transl Med JT - Journal of translational medicine JID - 101190741 RN - 0 (RNA, Long Noncoding) RN - 0 (Transforming Growth Factor beta1) RN - 0 (Transforming Growth Factor beta) SB - IM MH - Mice MH - Animals MH - *RNA, Long Noncoding/genetics/metabolism MH - In Situ Hybridization, Fluorescence MH - Liver Cirrhosis/genetics/metabolism MH - Hepatic Stellate Cells MH - Fibrosis MH - Transforming Growth Factor beta1/metabolism MH - Transforming Growth Factor beta/metabolism MH - Liver/metabolism PMC - PMC10621198 OTO - NOTNLM OT - Apoptosis OT - Fam98b OT - Gm9866 OT - Liver fibrosis OT - lncRNA COIS- The authors have declared no conflict of interest. EDAT- 2023/11/03 06:44 MHDA- 2023/11/06 06:42 PMCR- 2023/11/02 CRDT- 2023/11/03 00:55 PHST- 2023/08/03 00:00 [received] PHST- 2023/10/20 00:00 [accepted] PHST- 2023/11/06 06:42 [medline] PHST- 2023/11/03 06:44 [pubmed] PHST- 2023/11/03 00:55 [entrez] PHST- 2023/11/02 00:00 [pmc-release] AID - 10.1186/s12967-023-04642-1 [pii] AID - 4642 [pii] AID - 10.1186/s12967-023-04642-1 [doi] PST - epublish SO - J Transl Med. 2023 Nov 2;21(1):778. doi: 10.1186/s12967-023-04642-1.