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lncRNA GAS5 restrains CCl4-induced hepatic fibrosis by targeting miR-23a through the PTEN/PI3K/Akt signaling pathway.
Am J Physiol Gastrointest Liver Physiol. 2019 04 01; 316(4):G539-G550.AJ

Abstract

Hepatic fibrosis is chronic liver damage with many causes that has a relatively high death rate. The current study showed that long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5), microRNA-23a (miR-23a), and phosphatase and tensin homolog (PTEN) play important roles in the pathological process of hepatic fibrosis but have a relatively unclear regulatory mechanism. This study aimed to investigate the roles of lncRNA GAS5, miR-23a, and PTEN in the pathological process of hepatic fibrosis and hepatic stellate cell (HSC) activation. We used carbon tetrachloride (CCl4) intraperitoneal injections to establish a rat hepatic fibrosis model and exogenous transforming growth factor-β1 to establish an HSC activation model. Quantitative RT-PCR, Western blot, dual-luciferase reporter system, and RNA pull-down assays were used to investigate which microRNAs and lncRNAs participate in the process of hepatic fibrosis and HSC activation. miR-23a expression increased significantly in hepatic fibrosis tissues and activated HSCs. miR-23a interaction with and degradation of PTEN further influenced the downstream signaling pathway phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin/Snail (PI3K/Akt/mTOR/Snail), causing E-cadherin expression levels to decrease and α-smooth muscle actin and collagen I expression levels to increase. lncRNA GAS5 can be used as a sponge platform for miR-23a to decrease miR-23a expression levels competitively. We revealed the role of the lncRNA GAS5/miR-23a/PTEN/PI3K/Akt/mTOR/Snail signaling pathway in hepatic fibrosis, providing molecular targets for the treatment of hepatic fibrosis. NEW & NOTEWORTHY This is the first study revealing that microRNA-23a (miR-23a) promotes hepatic fibrosis through the phosphatase and tensin homolog/phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin/Snail signaling pathway, and long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) can act as a sponge platform for miR-23a. Therefore, lncRNA GAS5/miR-23a may bring molecular targets for hepatic fibrosis therapy.

Authors+Show Affiliations

Department of Pharmacy, Affiliated Hospital of Inner Mongolia Medical University , Hohhot, Inner Mongolia , People's Republic of China.Department of Pharmacy, Affiliated Hospital of Inner Mongolia Medical University , Hohhot, Inner Mongolia , People's Republic of China.Department of Pharmacy, Affiliated Hospital of Inner Mongolia Medical University , Hohhot, Inner Mongolia , People's Republic of China.College of Traditional Mongolia Medicine, Inner Mongolia Medical University , Hohhot, Inner Mongolia , People's Republic of China.Department of Pharmacy, Affiliated Hospital of Inner Mongolia Medical University , Hohhot, Inner Mongolia , People's Republic of China.Department of Pharmacy, Affiliated Hospital of Inner Mongolia Medical University , Hohhot, Inner Mongolia , People's Republic of China.College of Traditional Mongolia Medicine, Inner Mongolia Medical University , Hohhot, Inner Mongolia , People's Republic of China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30735452

Citation

Dong, Zhiheng, et al. "LncRNA GAS5 Restrains CCl4-induced Hepatic Fibrosis By Targeting miR-23a Through the PTEN/PI3K/Akt Signaling Pathway." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 316, no. 4, 2019, pp. G539-G550.
Dong Z, Li S, Wang X, et al. LncRNA GAS5 restrains CCl4-induced hepatic fibrosis by targeting miR-23a through the PTEN/PI3K/Akt signaling pathway. Am J Physiol Gastrointest Liver Physiol. 2019;316(4):G539-G550.
Dong, Z., Li, S., Wang, X., Si, L., Ma, R., Bao, L., & Bo, A. (2019). LncRNA GAS5 restrains CCl4-induced hepatic fibrosis by targeting miR-23a through the PTEN/PI3K/Akt signaling pathway. American Journal of Physiology. Gastrointestinal and Liver Physiology, 316(4), G539-G550. https://doi.org/10.1152/ajpgi.00249.2018
Dong Z, et al. LncRNA GAS5 Restrains CCl4-induced Hepatic Fibrosis By Targeting miR-23a Through the PTEN/PI3K/Akt Signaling Pathway. Am J Physiol Gastrointest Liver Physiol. 2019 04 1;316(4):G539-G550. PubMed PMID: 30735452.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - lncRNA GAS5 restrains CCl4-induced hepatic fibrosis by targeting miR-23a through the PTEN/PI3K/Akt signaling pathway. AU - Dong,Zhiheng, AU - Li,Sha, AU - Wang,Xiaohui, AU - Si,Lengge, AU - Ma,Ruilian, AU - Bao,Lidao, AU - Bo,Agula, Y1 - 2019/02/08/ PY - 2019/2/9/pubmed PY - 2019/12/25/medline PY - 2019/2/9/entrez KW - HSC KW - PTEN/PI3K/Akt signal pathway KW - hepatic fibrosis KW - lncRNA GAS5 KW - miR-23a SP - G539 EP - G550 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am. J. Physiol. Gastrointest. Liver Physiol. VL - 316 IS - 4 N2 - Hepatic fibrosis is chronic liver damage with many causes that has a relatively high death rate. The current study showed that long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5), microRNA-23a (miR-23a), and phosphatase and tensin homolog (PTEN) play important roles in the pathological process of hepatic fibrosis but have a relatively unclear regulatory mechanism. This study aimed to investigate the roles of lncRNA GAS5, miR-23a, and PTEN in the pathological process of hepatic fibrosis and hepatic stellate cell (HSC) activation. We used carbon tetrachloride (CCl4) intraperitoneal injections to establish a rat hepatic fibrosis model and exogenous transforming growth factor-β1 to establish an HSC activation model. Quantitative RT-PCR, Western blot, dual-luciferase reporter system, and RNA pull-down assays were used to investigate which microRNAs and lncRNAs participate in the process of hepatic fibrosis and HSC activation. miR-23a expression increased significantly in hepatic fibrosis tissues and activated HSCs. miR-23a interaction with and degradation of PTEN further influenced the downstream signaling pathway phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin/Snail (PI3K/Akt/mTOR/Snail), causing E-cadherin expression levels to decrease and α-smooth muscle actin and collagen I expression levels to increase. lncRNA GAS5 can be used as a sponge platform for miR-23a to decrease miR-23a expression levels competitively. We revealed the role of the lncRNA GAS5/miR-23a/PTEN/PI3K/Akt/mTOR/Snail signaling pathway in hepatic fibrosis, providing molecular targets for the treatment of hepatic fibrosis. NEW & NOTEWORTHY This is the first study revealing that microRNA-23a (miR-23a) promotes hepatic fibrosis through the phosphatase and tensin homolog/phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin/Snail signaling pathway, and long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) can act as a sponge platform for miR-23a. Therefore, lncRNA GAS5/miR-23a may bring molecular targets for hepatic fibrosis therapy. SN - 1522-1547 UR - https://www.unboundmedicine.com/medline/citation/30735452/lncRNA_GAS5_restrains_CCl4_induced_hepatic_fibrosis_by_targeting_miR_23a_through_the_PTEN/PI3K/Akt_signaling_pathway_ L2 - http://www.physiology.org/doi/full/10.1152/ajpgi.00249.2018?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -