乙醇应答性 lnc171 通过 miR-873-5p/ZEB1 轴促进 HCC 细胞的迁移和侵袭。

Ethanol responsive lnc171 promotes migration and invasion of HCC cells via mir-873-5p/ZEB1 axis.

机构信息

School of Public Health, Guangxi Medical University, Nanning, 530021, China.

School of Public Health, Guilin Medical School, Guilin, 541199, China.

出版信息

BMC Cancer. 2024 May 1;24(1):550. doi: 10.1186/s12885-024-12309-3.

DOI:10.1186/s12885-024-12309-3

PMID:38693503

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11064308/

Abstract

BACKGROUNDS

Long nonconding RNAs (lncRNAs) have been found to be a vital regulatory factor in the development process of human cancer, and could regarded as diagnostic or prognostic biomarkers for human cancers. Here, we aim to confirm the expression and molecular mechanism of RP11-171K16.5 (lnc171) in hepatocellular carcinoma (HCC).

METHODS

Screening of differentially expressed lncRNAs by RNA sequencing. Expression level of gene was studied by quantitative real-time PCR (qRT-PCR). The effects of lnc171, mir-873-5p, and ethanol on migration and invasion activity of cells were studied used transwell assay, and luciferase reporter assay was used to confirm the binding site.

RESULTS

RNA sequencing showed that lnc171 was markedly up-regulated in HCC. siRNA-mediated knockdown of lnc171 repressed the migration and invasion ability of HCC cells. Bioinformatic analysis, dual luciferase reporter assay, and qRT-PCR indicated that lnc171 interacted with mir-873-5p in HCC cells, and Zin-finger E-box binding homeobox (ZEB1) was a downstream target gene of mir-873-5p. In addition, lnc171 could enhance migration and invasion ability of HCC cells by up-regulating ZEB1 via sponging mir-873-5p. More interestingly, ethanol stimulation could up-regulate the increase of lnc171, thereby regulating the expression of competing endogenous RNA (ceRNA) network factors which lnc171 participated in HCC cells.

CONCLUSIONS

Our date demonstrates that lnc171 was a responsive factor of ethanol, and plays a vital role in development of HCC via binding of mir-873-5p.

摘要

背景

长非编码 RNA（lncRNAs）已被发现是人类癌症发展过程中的一个重要调节因子，可作为人类癌症的诊断或预后生物标志物。在这里，我们旨在确认 RP11-171K16.5（lnc171）在肝细胞癌（HCC）中的表达和分子机制。

方法

通过 RNA 测序筛选差异表达的 lncRNAs。通过定量实时 PCR（qRT-PCR）研究基因的表达水平。使用 Transwell 测定法研究 lnc171、mir-873-5p 和乙醇对细胞迁移和侵袭活性的影响，并使用荧光素酶报告基因测定法确认结合位点。

结果

RNA 测序显示 lnc171 在 HCC 中明显上调。siRNA 介导的 lnc171 敲低抑制 HCC 细胞的迁移和侵袭能力。生物信息学分析、双荧光素酶报告基因测定和 qRT-PCR 表明 lnc171 在 HCC 细胞中与 mir-873-5p 相互作用，Zin-finger E-box 结合同源盒（ZEB1）是 mir-873-5p 的下游靶基因。此外，lnc171 可以通过海绵作用于 mir-873-5p 而上调 ZEB1，从而增强 HCC 细胞的迁移和侵袭能力。更有趣的是，乙醇刺激可以上调 lnc171 的增加，从而调节 lnc171 参与的 HCC 细胞竞争内源性 RNA（ceRNA）网络因子的表达。