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中国癌症防治杂志

中国癌症防治杂志 ›› 2022, Vol. 14 ›› Issue (5): 496-502.doi: 10.3969/j.issn.1674?5671.2022.05.04

• 基础研究 • 上一篇    下一篇

miR⁃29a⁃3p靶向KDM5B调控肾透明细胞癌增殖和侵袭

  

  1. 武警特色医学中心 急诊医学科，研究部 
  • 出版日期:2022-10-25 发布日期:2022-11-09
  • 通讯作者: 胡金朋 E?mail：zzjj13@yeah.net
  • 基金资助:
    国家重点研发计划项目（2017YFC1307602）；武警后勤部应用基础研究项目（CWJ18L004）

miR⁃29a⁃3p inhibits the proliferation and invasion of kidney renal clear cell carcinoma by regulating the expression of KDM5B

  • Online:2022-10-25 Published:2022-11-09

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摘要： 目的 探究miR-29a-3p 通过调控赖氨酸特异性去甲基化酶5B （lysine-specific demethylase 5B，KDM5B）的表达对肾透明细胞癌（kidney renal clear cell carcinoma，KIRC）增殖和侵袭的影响及临床意义。方法 通过TCGA数据库数据分析不同分期KIRC患者中KDM5B的表达情况及对KIRC预后生存的影响；并利用TCGA数据分析不同分期KIRC患者中miR-29a-3p的表达情况及与KDM5B表达的相关性。采用脂质体转染技术分别将miR-29a-3p mimics、mimics-NC和miR-29a-3p inhibitor转染到KIRC 786-O和Caki-1细胞中，并定义为miR-29a mimic组、mimics NC组和Inhibitor组，采用RT-qPCR检测miR-29a-3p和KDM5B的表达水平，MTS检测细胞增殖能力，Transwell检测细胞侵袭能力。利用双荧光素酶报告基因实验验证miR-29a-3p和KDM5B的靶向关系。结果 TCGA数据库分析结果显示，不同分期KIRC患者中KDM5B的表达差异最明显，KDM5B明显影响KIRC患者的预后（HR=2.882，P<0.001）。与KDM5B结合的miR-29a-3p在不同分期KIRC患者中表达差异最明显（P<0.001），且与KDM5B相关性最强（r=-0.283，P<0.001）。双荧光素酶报告基因实验证实miR-29a-3p可与KDM5B特异结合。过表达miR-29a-3p后，786-O、Caki-1细胞中KDM5B表达水平下调，细胞增殖能力下降，穿膜细胞数减少（均P<0.05）；沉默miR-29a-3p后，KDM5B表达水平上调，细胞增殖能力升高，穿膜细胞数增多（均P<0.05）。结论 miR-29a-3p可能通过下调H3K4去甲基化酶KDM5B的表达抑制KIRC细胞系786-O、Caki-1的增殖和侵袭。

关键词: 肾透明细胞癌, miR-29a-3p, 赖氨酸特异性去甲基化酶5B, 增殖, 侵袭

Abstract: Objective To investigate the effect of miR?29a?3p on the proliferation and invasion of kidney renal clear cell carcinoma (KIRC) by regulating the expression of lysine?specific demethylase 5B (KDM5B) and its clinical significance. Methods The expression of KDM5B in patients with different KIRC stages and its impact on the prognosis and survival of KIRC were analyzed by using TCGA database. TCGA data were used to analyze the expression of miR?29a?3p in patients with different KIRC stages and its correlation with KDM5B. The miR?29a?3p mimics, mimics?NC and miR?29a?3p inhibitor, denoted by miR?29a mimic group, mimics NC group and inhibitor group, respectively, were transfected into KIRC 786?O and Caki?1 cells, respectively, by liposome transfection technology. The expre?ssion levels of miR?29a?3p and KDM5B were detected by RT?qPCR. The cell proliferation ability was detected by MTS, and the cell invasion ability was detected by transwell. Dual luciferase reporter assay was used to verify the targeting relationship between miR?29a?3p and KDM5B. Results TCGA database analysis showed that the expression of KDM5B differed most among the patients with different KIRC stages, which were significantly affected the prognosis of KIRC patients (HR=2.882, P<0.001). The expression of miR?29a?3p bound to KDM5B was most different among the patients with different KIRC stages (P<0.001), and had the strongest correlation with KDM5B (r=-0.283, P<0.001). Dual luciferase reporter assay confirmed that miR?29a?3p was specifically bound to KDM5B. After overexpression of miR?29a?3p, the expression level of KDM5B was down?regulated in 786?O and Caki?1 cells, and the cell proliferation ability and the number of transmembrane cells were decreased (all P<0.05). After miR?29a?3p silencing, the expression level of KDM5B was up?regulated, and the cell proliferation ability and the number of transmembrane cells were increased (all P<0.05). Conclusions miR?29a?3p may inhibit the proliferation and invasion of KIRC cell lines 786?O and Caki?1 by inhibiting the expression of H3K4 demethylase KDM5B.

Key words: Kidney renal clear cell carcinoma, miR?29a?3p, KDM5B, Proliferation, Invasion

中图分类号: 

  • R734.2