长链非编码RNA GIHCG通过调控miR-499a-5p/XIAP轴促进肾细胞癌的增殖和迁移。
LncRNA GIHCG promoted the proliferation and migration of renal cell carcinoma through regulating miR-499a-5p/XIAP axis.
作者信息
Zhu Shu-Ying, Zou Hong-Chang, Gao Ming-Ming, Chen Yan-Xia, Xu Man, Qin Xiao-Hua
机构信息
Department of Nephrology, The Second Affiliated Hospital of Nanchang University, No.1, Minde Road, Nanchang, Jiangxi 330006, PR China.
Department of Nephrology, The Second Affiliated Hospital of Nanchang University, No.1, Minde Road, Nanchang, Jiangxi 330006, PR China.
出版信息
Transl Oncol. 2022 Jun;20:101356. doi: 10.1016/j.tranon.2022.101356. Epub 2022 Mar 24.
BACKGROUND
Our previous study demonstrated that lncRNA GIHCG is upregulated in renal cell carcinoma (RCC) and that knockdown of lncRNA GIHCG suppresses the proliferation and migration of RCC cells. However, the mechanism of lncRNA GIHCG in RCC needs further exploration.
METHODS
The proliferation, cell cycle, migration, and apoptosis of RCC cells were tested using CCK-8, flow cytometry, wound healing and Annexin-V/-FITC/PI flow cytometry assays, respectively. Dual-luciferase reporter and RNA pull-down or RNA immunoprecipitation assays (RIPs) were performed to analyze the interactions among lncRNA GIHCG, miR-499a-5p and XIAP. A tumour xenograft study was conducted to verify the function of lncRNA GIHCG in RCC development in vivo.
RESULTS
Knockdown of lncRNA GIHCG inhibited cell proliferation and migration and induced G0/G1 arrest while promoting apoptosis. Overexpression of lncRNA GIHCG led to the opposite results. LncRNA GIHCG sponged miR-499a-5p and downregulated its expression in RCC cells. MiR-499a-5p overexpression suppressed RCC cell growth. MiR-499a-5p targeted XIAP and inhibited its expression. LncRNA GIHCG knockdown reduced the growth of tumour xenografts in vivo and the expression of XIAP while increasing miR-499a-5p levels.
CONCLUSION
LncRNA GIHCG accelerated the development of RCC by targeting miR-499a-5p and increasing XIAP levels.
背景
我们之前的研究表明，长链非编码RNA GIHCG在肾细胞癌（RCC）中上调，并且敲低长链非编码RNA GIHCG可抑制RCC细胞的增殖和迁移。然而，长链非编码RNA GIHCG在RCC中的作用机制仍需进一步探索。
方法
分别使用CCK-8、流式细胞术、伤口愈合实验和Annexin-V/-FITC/PI流式细胞术检测RCC细胞的增殖、细胞周期、迁移和凋亡情况。进行双荧光素酶报告基因检测以及RNA下拉或RNA免疫沉淀实验（RIP），以分析长链非编码RNA GIHCG、miR-499a-5p和XIAP之间的相互作用。开展肿瘤异种移植研究，以在体内验证长链非编码RNA GIHCG在RCC发生发展中的作用。
结果
敲低长链非编码RNA GIHCG可抑制细胞增殖和迁移，诱导G0/G1期阻滞，同时促进细胞凋亡。过表达长链非编码RNA GIHCG则导致相反的结果。长链非编码RNA GIHCG可吸附miR-499a-5p并下调其在RCC细胞中的表达。过表达miR-499a-5p可抑制RCC细胞生长。miR-499a-5p靶向XIAP并抑制其表达。敲低长链非编码RNA GIHCG可降低体内肿瘤异种移植瘤的生长以及XIAP的表达，同时提高miR-499a-5p水平。
结论
长链非编码RNA GIHCG通过靶向miR-499a-5p并提高XIAP水平来加速RCC的发展。
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