MicroRNA-370 inhibits the growth and metastasis of lung cancer by down-regulating epidermal growth factor receptor expression

Autor: Jia-Gui Ye, Xiao-qun Chen, Xicai Wang, You-Guang Huang, Mei Li, Congguo Jin, Jia Li, Min Lan, Yan Chen, Qian Yao, Yongchun Zhou, Xin Liu, Ke Li
Rok vydání: 2016
Předmět:
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: // Xin Liu 1, * , You-Guang Huang 1, * , Cong-Guo Jin 1 , Yong-Chun Zhou 1 , Xiao-Qun Chen 1 , Jia Li 1 , Yan Chen 1 , Mei Li 2 , Qian Yao 1 , Ke Li 3 , Min Lan 1 , Jia-Gui Ye 1 and Xi-Cai Wang 1 1 Tumor Institute, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, China 2 Pathological Department, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, China 3 The Second Oncology Department, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, China * These authors have contributed equally to this work Correspondence to: Xi-Cai Wang, email: wangxc2005323@126.com Keywords: lung cancer, mir-370, EGFR, proliferation, metastasis Received: December 23, 2016 Accepted: July 25, 2017 Published: October 04, 2017 ABSTRACT Abnormal microRNA-370 (miR-370) expression has been frequently reported in several types of cancers, including lung cancer. However, the role and molecular mechanisms of miR-370 in regulating the growth and metastasis of lung cancer have not been clarified. Here, we show higher levels of epidermal growth factor receptor (EGFR), but lower levels of miR-370 expression in most human lung cancer cells and non-tumor cells. Induction of miR-370 over-expression significantly reduced the levels of EGFR expression and the EGFR 3’untranslated region (UTR)-regulated luciferase activity in XWLC-05 and H157 cells, suggesting that miR-370 may bind to the 3’UTR of EGFR mRNA. Compared with the control cells, induction of miR370 overexpression significantly inhibited the proliferation, clone formation capacity, migration and invasion of XWLC-05 and H157 cells while miR-370 inhibitor over-expression enhanced their tumor behaviors in vitro . Furthermore, miR-370 over-expression down-regulated the EGFR and hypoxia-inducible factor (HIF)-1α expression, and attenuated the extracellular single-regulated kinase (ERK)1/2 and AKT phosphorylation in XWLC-05 and H157 cells. In contrast, miR370 inhibitor over-expression increased the EGFR and HIF-1α expression as well as the ERK1/2 and AKT phosphorylation in XWLC-05 and H157 cells. Moreover, miR-370 over-expression significantly reduced the levels of EGFR and CD31 expression and inhibited the growth and lung metastasis of xenograft NSCLC tumors in mice. Our study indicates that miR-370 may bind to the 3’UTR of EGFR to inhibit EGFR expression and the growth, angiogenesis and metastasis of non-small cell lung cancer by down-regulating the ERK1/2 and AKT signaling.
Databáze: OpenAIRE