Long non‐coding RNAs (lncRNAs) take various biological effects in clear cell renal cell carcinoma (ccRCC) mostly through sponging with microRNAs (miRNAs). lncRNA MIR4435‐2HG is found to promote tumour progression in gastric cancer, glioblastoma and hepatocellular carcinoma. However, the role of lncRNA MIR4435‐2HG in ccRCC progression remains unknown. The purpose of this research was to investigate the potential molecular mechanism of lncRNA MIR4435‐2HG regarding the regulation of ccRCC initiation and progression. In this study, we found the up‐regulation of MIR4435‐2HG in ccRCC tissues and cell lines. Functionally, overexpression of MIR4435‐2HG promoted the proliferation as well as the metastasis in ccRCC cell lines, whereas knockdown of MIR4435‐2HG inhibited the above changes. Then, bioinformatic analysis and luciferase reporter assays confirmed the negative regulation effect of MIR4435‐2HG on miR‐513a‐5p. And further investigations showed that KLF6, which collected from the intersection of databases, was the potential conjugated mRNAs of miR‐513a‐5p. Finally, the rescue experiments revealed the relation among MIR4435‐2HG and KLF6, which showed that KLF6 could reverse the promoting effect of MIR4435‐2HG on ccRCC in vitro and in vivo. Therefore, our findings provided insight into the mechanisms of MIR4435‐2HG in ccRCC and revealed an alternative target for the clinical diagnosis and treatment of ccRCC.

中文翻译：

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lncRNA MIR4435-2HG通过miR-513a-5p/KLF6轴促进透明细胞肾细胞癌恶性进展


长非编码 RNA (lncRNA) 在透明细胞肾细胞癌 (ccRCC) 中主要通过微小 RNA (miRNA) 的海绵作用发挥各种生物学作用。研究发现 lncRNA MIR4435-2HG 可促进胃癌、胶质母细胞瘤和肝细胞癌的肿瘤进展。然而，lncRNA MIR4435-2HG 在 ccRCC 进展中的作用仍不清楚。本研究的目的是探讨 lncRNA MIR4435-2HG 调节 ccRCC 发生和进展的潜在分子机制。在这项研究中，我们发现 MIR4435-2HG 在 ccRCC 组织和细胞系中上调。从功能上讲，MIR4435-2HG 的过表达促进了 ccRCC 细胞系的增殖和转移，而 MIR4435-2HG 的敲低则抑制了上述变化。然后，生物信息学分析和荧光素酶报告基因检测证实了 MIR4435-2HG 对 miR-513a-5p 的负调控作用。进一步的研究表明，从数据库交叉收集的 KLF6 是 miR-513a-5p 的潜在缀合 mRNA。最后，拯救实验揭示了MIR4435-2HG和KLF6之间的关系，表明KLF6可以逆转MIR4435-2HG在体外和体内对ccRCC的促进作用。因此，我们的研究结果深入了解了 MIR4435-2HG 在 ccRCC 中的作用机制，并揭示了 ccRCC 临床诊断和治疗的替代靶点。