Effects of microRNA-126 on cell proliferation, apoptosis and tumor angiogenesis via the down-regulating ERK signaling pathway by targeting EGFL7 in hepatocellular carcinoma
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Cheng Gong1, Jing Fang2, Guang Li2, Han-Han Liu3 and Zhi-Su Liu1
1Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R. China
2Department of Oncology, Wuhan Pu-Ai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430034, P.R. China
3Department of Pathology, Maternal and Child Health Hospital of Hubei Province, Wuhan 430070, P.R. China
Han-Han Liu, email: email@example.com
Zhi-Su Liu, email: firstname.lastname@example.org
Keywords: microRNA-126, epidermal growth factor-like domain 7 (EGFL7), hepatocellular carcinoma, ERK signaling pathway, proliferation
Received: October 12, 2016 Accepted: March 24, 2017 Published: April 20, 2017
This study intends to explore the effects of microRNA-126 (miR-126) on cell proliferation, apoptosis, and tumor angiogenesis in hepatocellular carcinoma (HCC) by regulating epidermal growth factor-like domain 7 (EGFL7) through extracellular signal-regulated kinase (ERK) signaling. HCC tissues and adjacent normal tissues were obtained from 184 HCC patients. HCC cells were separately transfected with recombinant plasmids. Western blotting and qRT-PCR were applied to detect miR-126 and EGFL7, ERK, Fas/FasL, Bcl-2, Caspase mRNA and protein levels. CCK8 and TUNEL were performed to determinate cell proliferation and apoptosis. Flow cytometry was used to analyze cell cycle distribution. Rats model of HCC was constructed, and tumor weight and the number of new blood vessels were recorded after 3 weeks of tumor transplantation. Compared with the adjacent normal tissues, HCC tissues exhibited lower miR-126 expression, and higher EGFL7, and ERK mRNA and protein levels. Overexpression of miR-126 in HCC cell lines suppressed EGFL7, ERK, Bcl-2, and P-ERK, and increased apoptotic-associated proteins Fas/FasL and Caspase-3, and it inhibited cell proliferation and induced cell apoptosis. Overexpression of miR-126 in nude mice resulted in reduced tumor weight and less new blood vessels in tumors. The inhibition of miR-126 decreased cell apoptosis, and enhanced cell proliferation and tumor angiogenesis. This study demonstrates that miR-126 might decrease cell proliferation, induce apoptosis, and inhibit tumor angiogenesis in HCC by inhibiting EGFL7 via down-regulating the ERK signaling pathway.
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