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miR-200c Accelerates Hepatic Stellate Cell-Induced Liver Fibrosis via Targeting the FOG2/PI3K Pathway.
Biomed Res Int. 2017; 2017:2670658.BR

Abstract

BACKGROUND

Although expression of miR-200s is aberrant in liver fibrosis, its role in liver fibrogenesis still remains unknown. Here, we investigated the role of miR-200c in the activation of human hepatic stellate cells (HSCs) and induction of liver fibrosis.

METHODS

We engineered human HSCs (LX2 cell line) to stably express miR-200c (LX2-200c) or empty vector control (LX2-nc).

RESULTS

miR-200c expression upregulated α-smooth muscle actin (SMA) and vimentin, enhanced HSCs growth and migration, increased expression of collagen type I (a main component of ECM) gene and secretion of epidermal growth factor (EGF), and upregulated the phosphorylation of Akt, a downstream effector of the PI3K pathway. As a target of miR-200s and inhibitor of PI3K pathway, FOG2 protein expression was significantly suppressed in LX2-200c cells. Moreover, LY294002, a highly selective inhibitor of PI3K, blocked phosphorylation of Akt and the effects of miR-200c.

CONCLUSIONS

These data suggest that miR-200c activates HSCs in liver fibrosis possibly by downregulating FOG2 protein expression and upregulating PI3K/Akt signaling. Autocrine activation of EGF signaling may also be a mechanism of miR-200c-mediated HSCs activation. So miR-200c can be a potential marker for HSCs activation and liver fibrosis progression, as well as a potential target to attenuate liver fibrosis.

Authors+Show Affiliations

Department of Liver Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.Department of Liver Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.Department of Biliary and Pancreatic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.School of Life Sciences, Sun Yat-sen University, Guangzhou 510080, China.Department of Liver Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28691020

Citation

Ma, Tengfei, et al. "MiR-200c Accelerates Hepatic Stellate Cell-Induced Liver Fibrosis Via Targeting the FOG2/PI3K Pathway." BioMed Research International, vol. 2017, 2017, p. 2670658.
Ma T, Cai X, Wang Z, et al. MiR-200c Accelerates Hepatic Stellate Cell-Induced Liver Fibrosis via Targeting the FOG2/PI3K Pathway. Biomed Res Int. 2017;2017:2670658.
Ma, T., Cai, X., Wang, Z., Huang, L., Wang, C., Jiang, S., Hua, Y., & Liu, Q. (2017). MiR-200c Accelerates Hepatic Stellate Cell-Induced Liver Fibrosis via Targeting the FOG2/PI3K Pathway. BioMed Research International, 2017, 2670658. https://doi.org/10.1155/2017/2670658
Ma T, et al. MiR-200c Accelerates Hepatic Stellate Cell-Induced Liver Fibrosis Via Targeting the FOG2/PI3K Pathway. Biomed Res Int. 2017;2017:2670658. PubMed PMID: 28691020.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - miR-200c Accelerates Hepatic Stellate Cell-Induced Liver Fibrosis via Targeting the FOG2/PI3K Pathway. AU - Ma,Tengfei, AU - Cai,Xiuqin, AU - Wang,Zifeng, AU - Huang,Li, AU - Wang,Chang, AU - Jiang,Songshan, AU - Hua,Yunpeng, AU - Liu,Quentin, Y1 - 2017/06/13/ PY - 2017/02/05/received PY - 2017/03/21/accepted PY - 2017/7/11/entrez PY - 2017/7/12/pubmed PY - 2018/3/31/medline SP - 2670658 EP - 2670658 JF - BioMed research international JO - Biomed Res Int VL - 2017 N2 - BACKGROUND: Although expression of miR-200s is aberrant in liver fibrosis, its role in liver fibrogenesis still remains unknown. Here, we investigated the role of miR-200c in the activation of human hepatic stellate cells (HSCs) and induction of liver fibrosis. METHODS: We engineered human HSCs (LX2 cell line) to stably express miR-200c (LX2-200c) or empty vector control (LX2-nc). RESULTS: miR-200c expression upregulated α-smooth muscle actin (SMA) and vimentin, enhanced HSCs growth and migration, increased expression of collagen type I (a main component of ECM) gene and secretion of epidermal growth factor (EGF), and upregulated the phosphorylation of Akt, a downstream effector of the PI3K pathway. As a target of miR-200s and inhibitor of PI3K pathway, FOG2 protein expression was significantly suppressed in LX2-200c cells. Moreover, LY294002, a highly selective inhibitor of PI3K, blocked phosphorylation of Akt and the effects of miR-200c. CONCLUSIONS: These data suggest that miR-200c activates HSCs in liver fibrosis possibly by downregulating FOG2 protein expression and upregulating PI3K/Akt signaling. Autocrine activation of EGF signaling may also be a mechanism of miR-200c-mediated HSCs activation. So miR-200c can be a potential marker for HSCs activation and liver fibrosis progression, as well as a potential target to attenuate liver fibrosis. SN - 2314-6141 UR - https://www.unboundmedicine.com/medline/citation/28691020/miR_200c_Accelerates_Hepatic_Stellate_Cell_Induced_Liver_Fibrosis_via_Targeting_the_FOG2/PI3K_Pathway_ L2 - https://dx.doi.org/10.1155/2017/2670658 DB - PRIME DP - Unbound Medicine ER -