microRNA-320b suppresses HNF4G and IGF2BP2 expression to inhibit angiogenesis and tumor growth of lung cancer
Yu‐Shui Ma, Bowen Shi, Junhong Guo, Jibin Liu, Xiao‐Li Yang, Rui Xin, Yi Shi, Dandan Zhang, Gai‐Xia Lu, Chengyou Jia, Huimin Wang, Pei‐Yao Wang, Huiqiong Yang, Jiajia Zhang, Wei Wu, Ping‐Sheng Cao, Yuzhen Yin, Li‐Peng Gu, Linlin Tian, Zhongwei Lv, Chunyan Wu, Gao‐Ren Wang, Fei Yu, Likun Hou, Geng-Xi Jiang, 大崎 往夫
Abstract
We examined the effect of microRNA-320b (miR-320b) on tumor growth and angiogenesis in lung cancer and also determined its downstream molecular mechanisms. Lung cancer tissues and adjacent non-cancerous tissues were collected from 66 patients with lung cancer. miR-320b expression was experimentally determined to be expressed at low level in cancer tissues. The results of gain-of-function experiments suggested that miR-320b overexpression suppressed cancer cell invasion, tube formation, tumor volume and angiogenesis in xenografted nude mice. Hepatocyte nuclear factor 4 gamma (HNF4G) was identified as a target of miR-320b based on in silico analysis. Dual-luciferase reporter gene assays further identified the binding relationship between HNF4G and miR-320b. Lung cancer tissues exhibited increased expression of HNF4G and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Meanwhile, HNF4G knockdown suppressed IGF2BP2 expression, thereby repressing cancer cell invasion and tube formation. Furthermore, IGF2BP2 modified m6A to increase the expression of thymidine kinase 1 (TK1), thus promoting angiogenesis. In nude mice, restoration of TK1 reversed the suppressive effect of miR-320b overexpression on tumor growth rate and CD31 expression. In conclusion, miR-320b suppresses lung cancer growth and angiogenesis by inhibiting HNF4G, IGF2BP2 and TK1.