A1BG-AS1 promotes the biological functions of osteosarcoma cells via regulating the microRNA-148a-3p/USP22 axis and stabilizing the expression of SIRT1 through deubiquitinase function.

IF 4.6 2区 医学 Q1 PHARMACOLOGY & PHARMACY Expert Opinion on Therapeutic Targets Pub Date : 2023-07-01 Epub Date: 2023-10-30 DOI:10.1080/14728222.2023.2263908
Xiuxin Han, Mengfan Yin, Chen Gong, Chao Zhang, Genbao Zhu, Mengxue Hu, Kemeng Tan, La Jiang, Guowen Wang, Lili Li
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Abstract

Background: The study aims to explore the role of A1BG antisense RNA 1 (A1BG-AS1), microRNA (miR)-148a-3p and ubiquitin-specific protease 22 (USP22) on osteosarcoma (OS) cell growth.

Research design & methods: A1BG-AS1, miR-148a-3p, USP22, and silent information regulator 2 homolog 1 (SIRT1) levels in OS tissues and cells were determined. The effects of A1BG-AS1, miR-148a-3p, and USP22 on the biological functions of OS cells were examined by functional assays. In vivo assay was conducted to observe the effect of A1BG-AS1 on OS growth in vitro. The relationship of A1BG-AS1, miR-148a-3p, and USP22 was analyzed by bioinformatics analysis, RNA-fluorescence in situ hybridization, luciferase activity, and RNA binding protein immunoprecipitation assays. The relation between USP22 and SIRT1 was evaluated by immunoprecipitation.

Results: A1BG-AS1 and USP22 were highly expressed, and miR-148a-3p was lowly expressed in OS tissues and cells. Down-regulation of A1BG-AS1 and USP22 or up-regulation of miR-148a-3p impaired the malignant behaviors of OS cells. A1BG-AS1 sponged miR-148a-3p, and miR-148a-3p targeted USP22, thereby inhibiting USP22 expression. Up-regulating USP22 reversed the A1BG-AS1 suppression-induced phenotypic inhibition of OS cells. USP22 affected the biological functions of OS cells by deubiquitinating SIRT1.

Conclusion: A1BG-AS1 facilitates the biological functions of OS cells via mediating the miR-148a-3p/USP22 axis.

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A1BG-AS1通过调节microRNA-148a-3p/USP22轴和通过去泛素酶功能稳定SIRT1的表达来促进骨肉瘤细胞的生物学功能。
背景:本研究旨在探讨A1BG反义RNA 1(A1BG-AS1)、微小RNA(miR)-148a-3p和泛素特异性蛋白酶22(USP22)在骨肉瘤(OS)细胞生长中的作用。研究设计和方法:测定OS组织和细胞中A1BG-AS1、miR-148a-3p、USP22和沉默信息调节因子2同源物1(SIRT1)的水平。通过功能测定检测A1BG-AS1、miR-148a-3p和USP22对OS细胞生物学功能的影响。通过体内实验观察A1BG-AS1对OS体外生长的影响。通过生物信息学分析、RNA荧光原位杂交、荧光素酶活性和RNA结合蛋白免疫沉淀分析A1BG-AS1、miR-148a-3p和USP22的关系。免疫沉淀法检测USP22与SIRT1的关系。结果:A1BG-AS1和USP22在OS组织和细胞中高表达,miR-148a-3p低表达。A1BG-AS1和USP22的下调或miR-148a-3p的上调损害了OS细胞的恶性行为。A1BG-AS1吸附miR-148a-3p,miR-148a-3 p靶向USP22,从而抑制USP22的表达。上调USP22逆转了A1BG-AS1抑制诱导的OS细胞表型抑制。USP22通过去泛素化SIRT1影响OS细胞的生物学功能。结论:A1BG-AS1通过介导miR-148a-3p/USP22轴促进OS细胞的生物功能。
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来源期刊
CiteScore
8.90
自引率
1.70%
发文量
58
审稿时长
3 months
期刊介绍: The journal evaluates molecules, signalling pathways, receptors and other therapeutic targets and their potential as candidates for drug development. Articles in this journal focus on the molecular level and early preclinical studies. Articles should not include clinical information including specific drugs and clinical trials. The Editors welcome: Reviews covering novel disease targets at the molecular level and information on early preclinical studies and their implications for future drug development. Articles should not include clinical information including specific drugs and clinical trials. Original research papers reporting results of target selection and validation studies and basic mechanism of action studies for investigative and marketed drugs. The audience consists of scientists, managers and decision makers in the pharmaceutical industry, academic researchers working in the field of molecular medicine and others closely involved in R&D.
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