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长链非编码RNA XIST通过调控miR-133a-5p/VEGFB促进口腔鳞状细胞癌(OSCC)细胞的恶性特征。

Long non-coding RNA XIST promotes the malignant features of oral squamous cell carcinoma (OSCC) cells through regulating miR-133a-5p/VEGFB.

作者信息

Wu Kankui, Wu Wancui, Wu Mengxuan, Liu Wenzhe

机构信息

Department of Stomatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Department of Stomatology, the First Affiliated Hospital of Jinan University, Jinan, China.

出版信息

Histol Histopathol. 2023 Jan;38(1):113-126. doi: 10.14670/HH-18-504. Epub 2022 Aug 1.

DOI:10.14670/HH-18-504
PMID:35912960
Abstract

OBJECTIVE

Oral squamous cell carcinoma (OSCC) represents a frequently seen oral cavity malignancy, and the mechanisms of its occurrence and development remain unclear. The present work examined the expression and biological function of long non-coding RNA (lncNRA) XIST (X-inactive specific transcript) in OSCC cells and tissues.

STUDY DESIGN

A total number of 50 OSCC and paired non-carcinoma tissue samples were collected in this study. Gene expression levels in cancer tissues and cells were quantified by RT-qPCR. In addition, gain- and loss-of-function experiments were conducted to investigate the biological roles of XIST as well as its downstream targets in OSCC cells.

RESULTS

XIST was upregulated in OSCC cells and tissues, which predicted a poorer prognostic outcome in OSCC patients. Silencing XIST inhibited the growth and invasion of OSCC cells and triggered apoptosis. miR-133a-5p was identified as a downstream target of XIST, which was downregulated in OSCC tissues. miR-133a-5p mediated the effect of XIST by targeting VEGFB. VEGFB overexpression rescued the inhibitory effects of XIST silencing on cell growth, invasion and migration.

CONCLUSION

Taken together, the above data indicates that XIST serves as an oncogenic factor to enhance the growth and invasion of OSCC cells by targeting the miR-133a/VEGFB axis.

摘要

目的

口腔鳞状细胞癌(OSCC)是一种常见的口腔恶性肿瘤,其发生和发展机制尚不清楚。本研究检测了长链非编码RNA(lncNRA)XIST(X染色体失活特异性转录本)在OSCC细胞和组织中的表达及生物学功能。

研究设计

本研究共收集了50例OSCC及配对的非癌组织样本。通过RT-qPCR定量检测癌组织和细胞中的基因表达水平。此外,进行了功能获得和功能缺失实验,以研究XIST及其下游靶点在OSCC细胞中的生物学作用。

结果

XIST在OSCC细胞和组织中上调,这预示着OSCC患者的预后较差。沉默XIST可抑制OSCC细胞的生长和侵袭并诱导凋亡。miR-133a-5p被鉴定为XIST的下游靶点,其在OSCC组织中表达下调。miR-133a-5p通过靶向VEGFB介导XIST的作用。VEGFB过表达可挽救XIST沉默对细胞生长、侵袭和迁移的抑制作用。

结论

综上所述,上述数据表明XIST作为一种致癌因子,通过靶向miR-133a/VEGFB轴增强OSCC细胞的生长和侵袭。