Tumor-promoting effects of microRNA-421/4-aminobutyrate aminotransferase axis in hepatocellular carcinoma

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 screen...

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Main Authors: Yuanguang Liu, Ran Cheng, Yijie Wu, Chunmei Liu, Yang Liu, Qing Chang, Jun Yin
Format: Article
Language:English
Published: Permanyer 2023-01-01
Series:Revista de Investigación Clínica
Subjects:
Online Access:https://www.clinicalandtranslationalinvestigation.com/frame_esp.php?id=474
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author Yuanguang Liu
Ran Cheng
Yijie Wu
Chunmei Liu
Yang Liu
Qing Chang
Jun Yin
author_facet Yuanguang Liu
Ran Cheng
Yijie Wu
Chunmei Liu
Yang Liu
Qing Chang
Jun Yin
author_sort Yuanguang Liu
collection DOAJ
description 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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spelling doaj.art-c7bd2016002d4bc4b713ab43469946b72023-11-02T21:08:58ZengPermanyerRevista de Investigación Clínica0034-83762564-88962023-01-0175510.24875/RIC.23000073Tumor-promoting effects of microRNA-421/4-aminobutyrate aminotransferase axis in hepatocellular carcinomaYuanguang Liu0Ran Cheng1Yijie Wu2Chunmei Liu3Yang Liu4Qing Chang5Jun Yin6Department of Hepatobiliary Surgery, Tangshan Gongren Hospital, Tangshan, ChinaDepartment of Hepatobiliary Surgery, Tangshan Gongren Hospital, Tangshan, ChinaDepartment of Hepatobiliary Surgery, Tangshan Gongren Hospital, Tangshan, ChinaDepartment of Hepatobiliary Surgery, Tangshan Gongren Hospital, Tangshan, ChinaDepartment of Hepatobiliary Surgery, Tangshan Gongren Hospital, Tangshan, ChinaDepartment of Head and Neck Surgery, Tangshan Gongren Hospital, Tangshan, ChinaDepartment of Hepatobiliary Surgery, Tangshan Gongren Hospital, Tangshan, ChinaBackground: 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. ( https://www.clinicalandtranslationalinvestigation.com/frame_esp.php?id=474Hepatocellular carcinoma. MicroRNA-421. 4-aminobutyrate aminotransferase. Cell phenotype. Epithelial-mesenchymal transition.
spellingShingle Yuanguang Liu
Ran Cheng
Yijie Wu
Chunmei Liu
Yang Liu
Qing Chang
Jun Yin
Tumor-promoting effects of microRNA-421/4-aminobutyrate aminotransferase axis in hepatocellular carcinoma
Revista de Investigación Clínica
Hepatocellular carcinoma. MicroRNA-421. 4-aminobutyrate aminotransferase. Cell phenotype. Epithelial-mesenchymal transition.
title Tumor-promoting effects of microRNA-421/4-aminobutyrate aminotransferase axis in hepatocellular carcinoma
title_full Tumor-promoting effects of microRNA-421/4-aminobutyrate aminotransferase axis in hepatocellular carcinoma
title_fullStr Tumor-promoting effects of microRNA-421/4-aminobutyrate aminotransferase axis in hepatocellular carcinoma
title_full_unstemmed Tumor-promoting effects of microRNA-421/4-aminobutyrate aminotransferase axis in hepatocellular carcinoma
title_short Tumor-promoting effects of microRNA-421/4-aminobutyrate aminotransferase axis in hepatocellular carcinoma
title_sort tumor promoting effects of microrna 421 4 aminobutyrate aminotransferase axis in hepatocellular carcinoma
topic Hepatocellular carcinoma. MicroRNA-421. 4-aminobutyrate aminotransferase. Cell phenotype. Epithelial-mesenchymal transition.
url https://www.clinicalandtranslationalinvestigation.com/frame_esp.php?id=474
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