Tumor-Promoting Effects of Microrna-421/4-Aminobutyrate Aminotransferase Axis in Hepatocellular Carcinoma.

Yuanguang Liu, Ran Cheng, Yijie Wu, Chunmei Liu, Yang Liu, Qing Chang, Jun Yin
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Abstract

Background: MicroRNA-421 (miR-421) has been implicated in hepatocellular carcinoma (HCC), but its potential mechanism in HCC remains unclear.

Objectives: The study aimed to study the potential mechanism of miR-421 in HCC which is necessary.

Methods: The downstream target genes of miR-421 were screened in HCC tissues and cells using miDIP, Targetscan, and starBase databases. Differential analysis, survival analysis, and Pearson correlation analysis were performed between miR-421 and its downstream target genes. Quantitative reverse transcription polymerase chain reaction and western blot were used to assay RNA and protein levels of 4-aminobutyrate aminotransferase (ABAT) and epithelial-mesenchymal transition (EMT)-related proteins. Cell-based assays, including CCK-8, wound healing, transwell, flow cytometry, and metabolic measurements, were implemented to assess proliferation, migration, invasion, cell cycle, and apoptosis of HCC cells with different treatments. Dual-luciferase assay was utilized to detect the targeting relationship between miR-421 and ABAT.

Results: miR-421 level was elevated in HCC tissues and cells, and low miR-421 expression hindered phenotype progression of HCC cells. ABAT was identified as a direct target of miR-421 in HCC cells, and miR-421 could inhibit ABAT expression. Rescue assay revealed that miR-421 promoted HCC cell tumorigenesis progress and affected cell metabolic remodeling through down-regulating ABAT.

Conclusion: The miR-421/ABAT regulatory axis promoted HCC cell tumorigenesis progress, highlighting its potential as a therapeutic target for HCC.

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Microrna-421/4氨基丁酸氨基转移酶轴在肝癌中的促瘤作用。
未分配:背景:微小RNA-421(miR-421)与肝细胞癌(HCC)有关,但其在HCC中的潜在机制尚不清楚。目的:本研究旨在研究miR-421在HCC中的潜在机制,这是必要的。方法:使用miDIP、Targetscan和starBase数据库在HCC组织和细胞中筛选miR-421的下游靶基因。在miR-421及其下游靶基因之间进行差异分析、生存分析和Pearson相关性分析。采用定量逆转录聚合酶链反应和蛋白质印迹法检测4-氨基丁酸氨基转移酶(ABAT)和上皮-间质转化(EMT)相关蛋白的RNA和蛋白质水平。基于细胞的测定,包括CCK-8、伤口愈合、transwell、流式细胞术和代谢测量,用于评估不同治疗的HCC细胞的增殖、迁移、侵袭、细胞周期和凋亡。利用双荧光素酶测定法检测miR-421和ABAT之间的靶向关系。结果:HCC组织和细胞中miR-421水平升高,低miR-421表达阻碍了HCC细胞的表型进展。ABAT被鉴定为miR-421在HCC细胞中的直接靶标,并且miR-421可以抑制ABAT的表达。拯救分析显示,miR-421通过下调ABAT促进HCC细胞的肿瘤发生进程并影响细胞代谢重塑。结论:miR-421/ABAT调控轴促进了HCC细胞的肿瘤发生,突出了其作为HCC治疗靶点的潜力。(REV-INVEST-CLIN.2023;75(5):233-48)。
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来源期刊
CiteScore
3.00
自引率
0.00%
发文量
60
审稿时长
>12 weeks
期刊介绍: The Revista de Investigación Clínica – Clinical and Translational Investigation (RIC-C&TI), publishes original clinical and biomedical research of interest to physicians in internal medicine, surgery, and any of their specialties. The Revista de Investigación Clínica – Clinical and Translational Investigation is the official journal of the National Institutes of Health of Mexico, which comprises a group of Institutes and High Specialty Hospitals belonging to the Ministery of Health. The journal is published both on-line and in printed version, appears bimonthly and publishes peer-reviewed original research articles as well as brief and in-depth reviews. All articles published are open access and can be immediately and permanently free for everyone to read and download. The journal accepts clinical and molecular research articles, short reports and reviews. Types of manuscripts: – Brief Communications – Research Letters – Original Articles – Brief Reviews – In-depth Reviews – Perspectives – Letters to the Editor
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