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长链非编码 RNA NEAT1 通过海绵吸附 miR-193a-3p 促进结直肠癌细胞的肿瘤发生。

LncRNA NEAT1 promotes the tumorigenesis of colorectal cancer by sponging miR-193a-3p.

机构信息

Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.

Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.

出版信息

Cell Prolif. 2019 Jan;52(1):e12526. doi: 10.1111/cpr.12526. Epub 2018 Nov 8.

Abstract

OBJECTIVES

LncRNA nuclear-enriched abundant transcript 1 (NEAT1) participates in the development and progression of multiple malignancies. However, the molecular mechanism by which NEAT1 contributes to colorectal cancer (CRC) remains unclear.

METHODS

The association between lncRNA NEAT1 expression and clinicopathological characteristics and prognosis in patients with CRC was analysed by TCGA RNA-sequencing data. MTT, colony formation, flow cytometry, transwell assays and a xenograft tumour model were used to assess the functions of NEAT1. Bioinformatics and spearman correlation analysis were used to identify the NEAT1-specific binding with miRNAs, and luciferase gene report and RIP assays were performed to confirm the interaction between miR-193a-3p (miR-193a) and NEAT1 in CRC cells.

RESULTS

Upregulation of NEAT1 expression was significantly correlated with TNM stage, poor survival and tumour recurrence in patients with CRC, and acted as an independent prognostic factor for tumour recurrence. Knockdown of NEAT1 suppressed cell proliferation, colony formation abilities and invasive potential and induced cell apoptosis, but overexpression of NEAT1 reversed these effects. Furthermore, NEAT1 was confirmed to act as a sponge of miR-193a, and knockdown of NEAT1 attenuated miR-193a inhibitor-induced tumour promoting effects and L17RD expression in CRC cells. miR-193a harboured negative correlation with NEAT1 and IL17RD expression in CRC specimens. In vivo experiment further validated the inhibitory effects of NEAT1 knockdown on xenograft tumour growth.

CONCLUSION

Our findings demonstrate that lncRNA NEAT1 acts as an oncogenic role in CRC cells by sponging miR-193a and may represent a potential marker for CRC patients.

摘要

目的

长链非编码 RNA 核富集丰富转录物 1(NEAT1)参与多种恶性肿瘤的发生和发展。然而,NEAT1 促进结直肠癌(CRC)的分子机制尚不清楚。

方法

通过 TCGA RNA 测序数据分析 lncRNA NEAT1 表达与 CRC 患者临床病理特征和预后的关系。MTT、集落形成、流式细胞术、transwell 检测和异种移植肿瘤模型用于评估 NEAT1 的功能。生物信息学和 spearman 相关性分析用于鉴定 NEAT1 与 miRNAs 的特异性结合,荧光素酶基因报告和 RIP 检测用于证实 miR-193a-3p(miR-193a)与 CRC 细胞中 NEAT1 的相互作用。

结果

CRC 患者中 NEAT1 表达上调与 TNM 分期、生存不良和肿瘤复发显著相关,并且是肿瘤复发的独立预后因素。敲低 NEAT1 抑制细胞增殖、集落形成能力和侵袭潜能并诱导细胞凋亡,但过表达 NEAT1 逆转了这些效应。此外,NEAT1 被证实是 miR-193a 的海绵体,敲低 NEAT1 减弱了 miR-193a 抑制剂诱导的 CRC 细胞中肿瘤促进作用和 L17RD 表达。miR-193a 与 CRC 标本中 NEAT1 和 IL17RD 表达呈负相关。体内实验进一步验证了敲低 NEAT1 对异种移植肿瘤生长的抑制作用。

结论

我们的研究结果表明,lncRNA NEAT1 通过海绵 miR-193a 在 CRC 细胞中发挥致癌作用,可能代表 CRC 患者的潜在标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c381/6430453/7193888bc0fb/CPR-52-e12526-g001.jpg

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