长链非编码 RNA XIST 通过作为 miR-200b-3p 的分子海绵来调节 ZEB1/2 表达,从而促进肝癌进展。

LncRNA XIST promotes liver cancer progression by acting as a molecular sponge of miR-200b-3p to regulate ZEB1/2 expression.

机构信息

Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Department of Medical Oncology, Zhejiang Provincial People's Hospital, People's Hospital Hangzhou Medical College, Zhejiang, China.

出版信息

J Int Med Res. 2021 May;49(5):3000605211016211. doi: 10.1177/03000605211016211.

Abstract

OBJECTIVE

To evaluate the predictive value of long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) for survival, and determine the involvement of miRNA(miR)-200b-3p and zinc finger E-box-binding homeobox (ZEB) 1/2 in the pro-tumor effect of lncRNA XIST in liver cancer.

METHODS

We evaluated lncRNA XIST expression in liver cancer tissues and cell lines by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and analyzed the correlation between its expression and overall survival of liver cancer patients by Kaplan-Meier analysis. Its effects on cell proliferation, migration, and invasion were analyzed by Cell-Counting Kit-8 and Transwell assays. The association between lncRNA XIST and miR-200b-3p, and the effects of lncRNA XIST on ZEB1/2 expression were explored using luciferase reporter assays, real-time PCR, and western blotting.

RESULTS

The lncRNA XIST was significantly upregulated in liver cancer, and increased lncRNA XIST expression was associated with a poor prognosis. The lncRNA XIST promoted liver cancer cell proliferation, migration, and invasion , and acted as a molecular sponge for miR-200b-3p, and also regulated the expression of ZEB1/2 via miR-200b-3p.

CONCLUSION

The lncRNA XIST is an oncogenic lncRNA that promotes liver cancer metastasis, and its pro-metastatic phenotype can be partially attributed to the lncRNA XIST/miR-200b-3p/ZEB1/2 signaling axis.

摘要

目的

评估长链非编码 RNA(lncRNA)X 失活特异性转录物(XIST)对生存的预测价值,并确定微小 RNA(miR)-200b-3p 和锌指 E 盒结合同源盒(ZEB)1/2 在 lncRNA XIST 促进肝癌肿瘤发生中的作用。

方法

通过定量逆转录聚合酶链反应(RT-qPCR)评估肝癌组织和细胞系中 lncRNA XIST 的表达,并通过 Kaplan-Meier 分析分析其表达与肝癌患者总生存的相关性。通过细胞计数试剂盒-8 和 Transwell 测定分析其对细胞增殖、迁移和侵袭的影响。利用荧光素酶报告实验、实时 PCR 和 Western blot 探讨 lncRNA XIST 与 miR-200b-3p 之间的关联以及 lncRNA XIST 对 ZEB1/2 表达的影响。

结果

lncRNA XIST 在肝癌中显著上调,lncRNA XIST 表达增加与预后不良相关。lncRNA XIST 促进肝癌细胞增殖、迁移和侵袭,作为 miR-200b-3p 的分子海绵,并通过 miR-200b-3p 调节 ZEB1/2 的表达。

结论

lncRNA XIST 是一种致癌的 lncRNA,促进肝癌转移,其促转移表型部分归因于 lncRNA XIST/miR-200b-3p/ZEB1/2 信号轴。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0be0/8142537/63fa272d9562/10.1177_03000605211016211-fig1.jpg

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