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lncRNA SATB2‑AS1的下调通过吸附miR‑671‑5p促进胶质瘤细胞增殖。

Downregulation of lncRNA SATB2‑AS1 facilitates glioma cell proliferation by sponging miR‑671‑5p.

作者信息

Gu Jia, Ye Yongqing, Sunil Rauniyar, Zhan Wenjian, Yu Rutong

机构信息

Department of Neurosurgery, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.

Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.

出版信息

Exp Ther Med. 2023 Sep 11;26(5):503. doi: 10.3892/etm.2023.12202. eCollection 2023 Nov.

Abstract

The antisense transcript of SATB2 protein (SATB2-AS1) is a novel long non-coding RNA (lncRNA) which is involved in the development of colorectal cancer, breast cancer and hepatocellular carcinoma. In the present study, it was aimed to investigate the consequent situation of SATB2-AS1 in tissue and cell lines of glioma. The expression of SATB2-AS1 in glioma cases was analyzed in The Cancer Genome Atlas datasets. The glycolytic metabolism was determined in glioma cells by detection of extracellular glucose level, oxygen consumption rate and extracellular acidification rate. Cell Counting Kit-8 assay and flow cytometry were used to assess cell proliferation and apoptosis in glioma cells. The interaction between SATB2-AS1 and microRNA (miR)-671-5p was verified by bioinformatic analysis, reverse transcription-quantitative PCR, dual luciferase reporter assay and RNA immunoprecipitation assay. The expression levels of the downstream targets of SATB2-AS1 were studied by western blotting. Results demonstrated that SATB2-AS1 was a downregulated lncRNA in low grade glioma and glioblastoma. Gain-of-function assay demonstrated that SATB2-AS1 inhibited cell proliferation, and glycolytic metabolism, while induced cell apoptosis in glioma cells. SATB2-AS1 sponged and suppressed the expression of an oncogenic miRNA miR-671-5p. By regulation of miR-671-5p, SATB2-AS1 upregulated cerebellar degeneration related protein 1 (CDR1) and Visinin-like 1 (VSNL1) expression in glioma cells. miR-671-5p overexpression partially reversed the antitumor effect of SATB2-AS1 in glioma. In conclusion, the current study demonstrated that there was a downregulation of SATB2-AS1 in glioma, and SATB2-AS1 regulated miR-671-5p/CDR1 axis and miR-671-5p/VSNL1 axis in glioma.

摘要

SATB2蛋白的反义转录本(SATB2-AS1)是一种新型长链非编码RNA(lncRNA),其参与了结直肠癌、乳腺癌和肝细胞癌的发生发展。在本研究中,旨在探究SATB2-AS1在胶质瘤组织和细胞系中的情况。通过癌症基因组图谱数据集分析SATB2-AS1在胶质瘤病例中的表达。通过检测细胞外葡萄糖水平、耗氧率和细胞外酸化率来测定胶质瘤细胞中的糖酵解代谢。使用细胞计数试剂盒-8法和流式细胞术评估胶质瘤细胞的增殖和凋亡。通过生物信息学分析、逆转录定量PCR、双荧光素酶报告基因检测和RNA免疫沉淀检测验证SATB2-AS1与微小RNA(miR)-671-5p之间的相互作用。通过蛋白质印迹法研究SATB2-AS1下游靶点的表达水平。结果表明,SATB2-AS1在低级别胶质瘤和胶质母细胞瘤中是一种下调的lncRNA。功能获得实验表明,SATB2-AS1抑制胶质瘤细胞的增殖和糖酵解代谢,同时诱导细胞凋亡。SATB2-AS1可吸附并抑制致癌miR-671-5p的表达。通过调控miR-671-5p,SATB2-AS1上调胶质瘤细胞中小脑变性相关蛋白1(CDR1)和类视锥蛋白样蛋白1(VSNL1)的表达。miR-671-5p过表达部分逆转了SATB2-AS1在胶质瘤中的抗肿瘤作用。总之,本研究表明胶质瘤中SATB2-AS1表达下调,且SATB2-AS1在胶质瘤中调控miR-671-5p/CDR1轴和miR-671-5p/VSNL1轴。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f0/10562957/2565448bff73/etm-26-05-12202-g00.jpg

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