Open AccessLong Noncoding RNA HOTTIP Promotes Mouse Hepatic Stellate Cell Activation via Downregulating miR-148a
Author(s) -
Zhiqin Li,
Jia Wang,
QingLei Zeng,
Chunling Hu,
Jiajia Zhang,
Hongyan Wang,
Jingya Yan,
Hua Li,
Zu-Jiang Yu
Publication year - 2018
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000496012
Subject(s) - hepatic stellate cell , downregulation and upregulation , long non coding rna , cancer research , in vivo , fibrosis , ccl4 , biology , liver cancer , hepatic fibrosis , in vitro , chemistry , medicine , endocrinology , gene , hepatocellular carcinoma , carbon tetrachloride , organic chemistry , biochemistry , microbiology and biotechnology
Background/Aims: HOTTIP is a critical modulator in human diseases including liver cancer, but its role and molecular biological mechanisms in liver fibrosis are still unclear. Methods: The expression profile of HOTTIP during the progression of liver fibrosis was detected in human liver samples and in CCl4-treated mice using qRT-PCR. The expressing sh-HOTTIP adenoviral vector was used to reduce HOTTIP levels in vivo. Dual-Luciferase Reporter Assay was performed to validate the interaction between miR-148a and HOTTIP, TGFBR1, or TGFBR2. Results: HOTTIP expressions in fibrotic liver samples and cirrhotic liver samples were significantly upregulated compared with healthy liver controls, and cirrhotic samples exhibited the highest levels of HOTTIP. Moreover, HOTTIP expressions were substantially induced in the liver tissues and hepatic stellate cells (HSC) of CCl4-treated mice. Ad-shHOTTIP delivery could alleviate CCl4- induced liver fibrosis in mice. Down-regulation of HOTTIP inhibited the viability and activation of HSCs in vitro, and HOTTIP negatively regulated miR-148a expression in HSCs. miR-148a had a negative effect on HSC activation by targeting TGFBR1 and TGFBR2. Conclusion: HOTTIP is involved in the progression of liver fibrosis by promoting HSC activation. The high level of HOTTIP downregulates miR-148a, thus to increase the level of TGFBR1 and TGFBR2 and contribute to liver fibrosis.