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Ma, Yu-Shui; Shi, Bo-Wen; Guo, Jun-Hong; Liu, Ji-Bin; Yang, Xiao-Li; Xin, Rui; Shi, Yi; Zhang, Dan-Dan; Lu, Gai-Xia; Jia, Cheng-You; Wang, Hui-Min; Wang, Pei-Yao; Yang, Hui-Qiong; Zhang, Jia-Jia; Wu, Wei; Cao, Ping-Sheng; Yin, Yu-Zhen; Gu, Li-Peng; Tian, Lin-Lin; Lv, Zhong-Wei; Wu, Chun-Yan; Wang, Gao-Ren; Yu, Fei; Hou, Li-Kun; Jiang, Geng-Xi; Fu, Da
Carcinogenesis (New York), 05/2021, Letnik: 42, Številka: 5Journal Article
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. miR-320b suppresses angiogenesis in lung cancer. miR-320b targets HNF4G and inhibits its expression. HNF4G increases IGF2BP2 expression to promote lung cancer. IGF2BP2 enhances the m6A modification of TK1 to promote lung cancer.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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