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长链非编码 RNA MIR4435-2HG 通过 miR-513a-5p/KLF6 轴促进肾透明细胞癌的恶性进展。

lncRNA MIR4435-2HG promoted clear cell renal cell carcinoma malignant progression via miR-513a-5p/KLF6 axis.

机构信息

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Department of Urology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

J Cell Mol Med. 2020 Sep;24(17):10013-10026. doi: 10.1111/jcmm.15609. Epub 2020 Jul 30.

DOI:10.1111/jcmm.15609
PMID:33460239
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7520272/
Abstract

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.

摘要

长链非编码 RNA（lncRNA）在透明细胞肾细胞癌（ccRCC）中通过与 microRNA（miRNA）结合发挥各种生物学效应。lncRNA MIR4435-2HG 已被发现可促进胃癌、胶质母细胞瘤和肝癌的肿瘤进展。然而，lncRNA MIR4435-2HG 在 ccRCC 进展中的作用尚不清楚。本研究旨在探讨 lncRNA MIR4435-2HG 在 ccRCC 发生和进展中的潜在分子机制。在这项研究中，我们发现 lncRNA MIR4435-2HG 在 ccRCC 组织和细胞系中上调。功能上，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实验证实了 MIR4435-2HG 对 miR-513a-5p 的负调控作用。进一步的研究表明，从数据库交集获得的 KLF6 是 miR-513a-5p 的潜在结合 mRNA。最后，挽救实验揭示了 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，我们的研究结果为 MIR4435-2HG 在 ccRCC 中的作用机制提供了深入的了解，并为 ccRCC 的临床诊断和治疗提供了另一种潜在的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/befd/7520272/f8025cde82dd/JCMM-24-10013-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/befd/7520272/e9c9571a88d9/JCMM-24-10013-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/befd/7520272/ddf11c3fe09d/JCMM-24-10013-g003.jpg
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