Yan Wang1, Daoquan Dong1, Shuqi Jiang1, Enpu Zhang1, Wenzhong Zheng1, Longyi Mao2, Weiqing Li1, Jingcheng Zhou1, Longlong Fan1, Ran Cheng1, Zesong Li2, Zhengyu Fang1, Yaoting Gui1, Xianxin Li1,3. 1. Department of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, China. 2. Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China. 3. Department of Surgical, Shenzhen Sun Yat-sen Cardiovascular Hospital, Shenzhen, China.
Abstract
BACKGROUND/AIMS: Increasing evidence has shown that miR-216b plays an important role in human cancer progression. However, little is known about the function of miR-216b in renal cell carcinoma. METHODS: The expression levels of miR-216b in renal cell carcinoma tissues and cell lines were examined by qRT-PCR. The biological role of miR-216b in renal cell carcinoma proliferation and/or metastasis was examined in vitro and in vivo. The target of miR-216b was identified by a dual-luciferase reporter assay. The expression level of KRAS protein was measured by western blotting. RESULTS: The expression of miR-216b was downregulated in clear cell renal cell carcinoma (ccRCC) cell lines and specimens compared to the adjacent normal tissues. Furthermore, miR-216b can bind to the 3'untranslated region (UTR) of KRAS and inhibit the expression of KRAS through translational repression. The in vitro study revealed that miR-216b attenuated ccRCC cell proliferation and invasion. Furthermore, in vivo study also showed that miR-216b suppressed tumor growth. MiR-216b exerted its tumor suppressor function through inhibiting the KRAS-related MAPK/ERK and PI3K/AKT pathways. CONCLUSION: Our findings provide, for the first time, significant clues regarding the role of miR-216b as a tumor suppressor by targeting KRAS in ccRCC.
BACKGROUND/AIMS: Increasing evidence has shown that miR-216b plays an important role in humancancer progression. However, little is known about the function of miR-216b in renal cell carcinoma. METHODS: The expression levels of miR-216b in renal cell carcinoma tissues and cell lines were examined by qRT-PCR. The biological role of miR-216b in renal cell carcinoma proliferation and/or metastasis was examined in vitro and in vivo. The target of miR-216b was identified by a dual-luciferase reporter assay. The expression level of KRAS protein was measured by western blotting. RESULTS: The expression of miR-216b was downregulated in clear cell renal cell carcinoma (ccRCC) cell lines and specimens compared to the adjacent normal tissues. Furthermore, miR-216b can bind to the 3'untranslated region (UTR) of KRAS and inhibit the expression of KRAS through translational repression. The in vitro study revealed that miR-216b attenuated ccRCC cell proliferation and invasion. Furthermore, in vivo study also showed that miR-216b suppressed tumor growth. MiR-216b exerted its tumor suppressor function through inhibiting the KRAS-related MAPK/ERK and PI3K/AKT pathways. CONCLUSION: Our findings provide, for the first time, significant clues regarding the role of miR-216b as a tumor suppressor by targeting KRAS in ccRCC.
Authors: Yingchen Zhou; Yang Zhang; Weiqing Li; Jinming Xu; Xia He; Xianxin Li; Yan Wang Journal: Cancer Manag Res Date: 2020-10-02 Impact factor: 3.989
Authors: Maíra Bianchi Rodrigues Alves; Rubens Paes de Arruda; Tiago Henrique Camara De Bem; Shirley Andrea Florez-Rodriguez; Manoel Francisco de Sá Filho; Clémence Belleannée; Flávio Vieira Meirelles; Juliano Coelho da Silveira; Felipe Perecin; Eneiva Carla Carvalho Celeghini Journal: Sci Rep Date: 2019-07-17 Impact factor: 4.379