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

较长的非编码RNA（lncRNA）在透明细胞肾细胞癌（ccRCC）中具有多种生物学效应，主要是通过与microRNA（miRNA）结合而实现的。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。但是，lncRNA MIR4435-2HG在ccRCC进展中的作用仍然未知。这项研究的目的是研究有关ccRCC起始和进展调控的lncRNA MIR4435- 2HG的潜在分子机制。在这项研究中，我们发现ccRCC组织和细胞系中MIR4435-2HG的上调。在功能上，MIR4435-2HG的过度表达促进了ccRCC细胞系的增殖以及转移，而MIR4435-2HG的抑制则抑制了上述变化。然后，生物信息学分析和萤光素酶报告基因分析证实了MIR4435-2HG对miR-513a-5p的负调节作用。进一步的研究表明，从数据库交叉点收集的KLF6是miR-513a-5p潜在的共轭mRNA。最后，救援实验揭示了MIR4435-2HG与KLF6之间的关系，这表明KLF6可以逆转MIR4435-2HG在体外和体内对ccRCC的促进作用。因此，我们的发现为ccRCC中MIR4435-2HG的机制提供了见识，并揭示了ccRCC的临床诊断和治疗的替代目标。救援实验揭示了MIR4435-2HG与KLF6之间的关系，这表明KLF6可以逆转MIR4435-2HG在体内和体外对ccRCC的促进作用。因此，我们的发现为ccRCC中MIR4435-2HG的机制提供了见识，并揭示了ccRCC的临床诊断和治疗的替代目标。救援实验揭示了MIR4435-2HG与KLF6之间的关系，表明KLF6可以逆转MIR4435-2HG在体内和体外对ccRCC的促进作用。因此，我们的发现为ccRCC中MIR4435-2HG的机制提供了见识，并揭示了ccRCC的临床诊断和治疗的替代目标。