Cargando…

Functional role and epithelial to mesenchymal transition of the miR-590-3p/MDM2 axis in hepatocellular carcinoma

BACKGROUND: There is considerable evidence that microRNAs (miRNAs) regulate several key tumor-associated genes/pathways and may themselves have a dual regulatory function either as tumor suppressors or oncogenic miRNA, depending on the tumor type. MicroRNA-590-3p (miR-590-3p) is a small non-coding R...

Descripción completa

Detalles Bibliográficos
Autores principales: Youssef, Alaa Ibrahem, Khaled, Gehad Mahmoud, Amleh, Asma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157954/
https://www.ncbi.nlm.nih.gov/pubmed/37138218
http://dx.doi.org/10.1186/s12885-023-10861-y
_version_ 1785036861942530048
author Youssef, Alaa Ibrahem
Khaled, Gehad Mahmoud
Amleh, Asma
author_facet Youssef, Alaa Ibrahem
Khaled, Gehad Mahmoud
Amleh, Asma
author_sort Youssef, Alaa Ibrahem
collection PubMed
description BACKGROUND: There is considerable evidence that microRNAs (miRNAs) regulate several key tumor-associated genes/pathways and may themselves have a dual regulatory function either as tumor suppressors or oncogenic miRNA, depending on the tumor type. MicroRNA-590-3p (miR-590-3p) is a small non-coding RNA involved in the initiation and progression of numerous tumors. However, its expression pattern and biological role in hepatocellular carcinoma (HCC) are controversial. RESULTS: In the current work, computational and RT-qPCR analysis revealed that HCC tissues and cell lines exhibited miR-590-3p downregulation. Forced expression of miR-590-3p attenuated HepG2 cells proliferation, migration, and repressed EMT-related gene expression. Bioinformatic, RT-qPCR, and luciferase assays revealed that MDM2 is a direct functional target of miR-590-3p. Moreover, the knockdown of MDM2 mimicked the inhibitory effect of miR-590-3p in HepG2 cells. CONCLUSION: We have identified not only novel targets for miR-590-3p in HCC, but also novel target genes for miR590-3p/MDM2 pathway in HCC like SNAIL, SLUG, ZEB1, ZEB2, and N-cadherin. Furthermore, these findings demonstrate a crucial role for MDM2 in the regulatory mechanism of EMT in HCC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10861-y.
format Online
Article
Text
id pubmed-10157954
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-101579542023-05-05 Functional role and epithelial to mesenchymal transition of the miR-590-3p/MDM2 axis in hepatocellular carcinoma Youssef, Alaa Ibrahem Khaled, Gehad Mahmoud Amleh, Asma BMC Cancer Research BACKGROUND: There is considerable evidence that microRNAs (miRNAs) regulate several key tumor-associated genes/pathways and may themselves have a dual regulatory function either as tumor suppressors or oncogenic miRNA, depending on the tumor type. MicroRNA-590-3p (miR-590-3p) is a small non-coding RNA involved in the initiation and progression of numerous tumors. However, its expression pattern and biological role in hepatocellular carcinoma (HCC) are controversial. RESULTS: In the current work, computational and RT-qPCR analysis revealed that HCC tissues and cell lines exhibited miR-590-3p downregulation. Forced expression of miR-590-3p attenuated HepG2 cells proliferation, migration, and repressed EMT-related gene expression. Bioinformatic, RT-qPCR, and luciferase assays revealed that MDM2 is a direct functional target of miR-590-3p. Moreover, the knockdown of MDM2 mimicked the inhibitory effect of miR-590-3p in HepG2 cells. CONCLUSION: We have identified not only novel targets for miR-590-3p in HCC, but also novel target genes for miR590-3p/MDM2 pathway in HCC like SNAIL, SLUG, ZEB1, ZEB2, and N-cadherin. Furthermore, these findings demonstrate a crucial role for MDM2 in the regulatory mechanism of EMT in HCC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10861-y. BioMed Central 2023-05-04 /pmc/articles/PMC10157954/ /pubmed/37138218 http://dx.doi.org/10.1186/s12885-023-10861-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Youssef, Alaa Ibrahem
Khaled, Gehad Mahmoud
Amleh, Asma
Functional role and epithelial to mesenchymal transition of the miR-590-3p/MDM2 axis in hepatocellular carcinoma
title Functional role and epithelial to mesenchymal transition of the miR-590-3p/MDM2 axis in hepatocellular carcinoma
title_full Functional role and epithelial to mesenchymal transition of the miR-590-3p/MDM2 axis in hepatocellular carcinoma
title_fullStr Functional role and epithelial to mesenchymal transition of the miR-590-3p/MDM2 axis in hepatocellular carcinoma
title_full_unstemmed Functional role and epithelial to mesenchymal transition of the miR-590-3p/MDM2 axis in hepatocellular carcinoma
title_short Functional role and epithelial to mesenchymal transition of the miR-590-3p/MDM2 axis in hepatocellular carcinoma
title_sort functional role and epithelial to mesenchymal transition of the mir-590-3p/mdm2 axis in hepatocellular carcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157954/
https://www.ncbi.nlm.nih.gov/pubmed/37138218
http://dx.doi.org/10.1186/s12885-023-10861-y
work_keys_str_mv AT youssefalaaibrahem functionalroleandepithelialtomesenchymaltransitionofthemir5903pmdm2axisinhepatocellularcarcinoma
AT khaledgehadmahmoud functionalroleandepithelialtomesenchymaltransitionofthemir5903pmdm2axisinhepatocellularcarcinoma
AT amlehasma functionalroleandepithelialtomesenchymaltransitionofthemir5903pmdm2axisinhepatocellularcarcinoma