Yue Yongjun, Cui Jinsheng, Zhao Yu, Liu Shangying, Niu Weixing
Department of Urology, Heji Hospital, Changzhi Medical College, Changzhi, Shanxi 046000, People's Republic of China.
Department of Ophthalmology, Peace Hospital, Changzhi Medical College, Changzhi, Shanxi 046000, People's Republic of China.
Cancer Manag Res. 2020 Dec 31;12:13513-13525. doi: 10.2147/CMAR.S272287. eCollection 2020.
Clear cell renal cell carcinoma (ccRCC) is one of the main subtypes of renal cell carcinoma, with intense aggressiveness. The involvement of circular RNAs (circRNAs) in human cancers attracts much concern. The intention of this study was to investigate the expression of circ_101341 and explore its function in ccRCC.
The expression of circ_101341, miR-411 and Egl nine homolog 3 () was measured using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was assessed by cell counting kit-8 (CCK-8) assay and colony formation assay. Cell migration and invasion were monitored by transwell assay. Xenograft model was established to explore the role of circ_101341 in vivo. The protein levels of E-cadherin (E-cad), N-cadherin (N-cad), matrix metalloprotein-9 (MMP9) and EGLN3 were detected by Western blot. Bioinformatic analysis was conducted using Circinteractome and starBase. The targeted relationship was verified using dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA pull-down assay.
The expression of circ_101341 was elevated in ccRCC tissues and cells. Functionally, circ_101341 knockdown depleted proliferation, migration and invasion of ccRCC cells in vitro and restricted tumor growth in vivo. Circ_101341 directly targeted miR-411, and miR-411 inhibition revised the inhibitory effects of circ_101341 knockdown on proliferation, migration and invasion in ccRCC cells. Moreover, miR-411 directly bound to EGLN3, and overexpression also rescued the effects of circ_101341 knockdown.
Circ_101341 functioned as a tumor promoter to strengthen proliferation, migration and invasion by regulating via sponging miR-411, indicating that circ_101341 was a potential diagnostic and therapeutic biomarker of ccRCC.
透明细胞肾细胞癌（ccRCC）是肾细胞癌的主要亚型之一，具有强烈的侵袭性。环状RNA（circRNAs）在人类癌症中的作用备受关注。本研究旨在调查circ_101341的表达，并探讨其在ccRCC中的功能。
采用定量实时聚合酶链反应（qRT-PCR）检测circ_101341、miR-411和Egl九同源物3（EGLN3）的表达。通过细胞计数试剂盒-8（CCK-8）测定法和集落形成测定法评估细胞增殖。通过Transwell测定法监测细胞迁移和侵袭。建立异种移植模型以探讨circ_101341在体内的作用。通过蛋白质印迹法检测E-钙黏蛋白（E-cad）、N-钙黏蛋白（N-cad）、基质金属蛋白酶-9（MMP9）和EGLN3的蛋白水平。使用Circinteractome和starBase进行生物信息学分析。使用双荧光素酶报告基因测定法、RNA结合蛋白免疫沉淀（RIP）测定法和RNA下拉测定法验证靶向关系。
circ_101341在ccRCC组织和细胞中的表达升高。在功能上，circ_101341敲低可降低ccRCC细胞在体外的增殖、迁移和侵袭能力，并在体内抑制肿瘤生长。circ_101341直接靶向miR-411，抑制miR-411可逆转circ_101341敲低对ccRCC细胞增殖、迁移和侵袭的抑制作用。此外，miR-411直接与EGLN3结合，EGLN3过表达也可挽救circ_101341敲低的影响。
circ_101341作为肿瘤促进因子，通过海绵吸附miR-411调节EGLN3，从而增强增殖、迁移和侵袭能力，表明circ_101341是ccRCC潜在的诊断和治疗生物标志物。
