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MiR-24-3p Inhibits the Progression of Pancreatic Ductal Adenocarcinoma Through LAMB3 Downregulation
Pancreatic ductal adenocarcinoma (PDAC) is associated with several genetic syndromes. However, the molecular mechanism underlying PDAC progression is still unknown. In this study, we showed that Laminin Subunit Beta 3 (LAMB3) was aberrantly overexpressed in PDAC and was closely associated with the o...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985431/ https://www.ncbi.nlm.nih.gov/pubmed/32039003 http://dx.doi.org/10.3389/fonc.2019.01499 |
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author | Huang, Wenjie Gu, Jianyou Tao, Tian Zhang, Junfeng Wang, Huaizhi Fan, Yingfang |
author_facet | Huang, Wenjie Gu, Jianyou Tao, Tian Zhang, Junfeng Wang, Huaizhi Fan, Yingfang |
author_sort | Huang, Wenjie |
collection | PubMed |
description | Pancreatic ductal adenocarcinoma (PDAC) is associated with several genetic syndromes. However, the molecular mechanism underlying PDAC progression is still unknown. In this study, we showed that Laminin Subunit Beta 3 (LAMB3) was aberrantly overexpressed in PDAC and was closely associated with the overall survival rate of patients with PDAC. Functional studies demonstrated that LAMB3 played important roles in cell proliferation, the cell cycle, and invasion capacity. Using bioinformatics analysis, we determined that miR-24-3p was an upstream miRNA of LAMB3, and further experiments verified that miR-24-3p regulated LAMB3 expression in PDAC cells. A dual-luciferase reporter system demonstrated that miR-24-3p directly targeted the LAMB3 3'UTR, and FISH assay confirmed that miR-24-3p and LAMB3 mRNA mostly resided in cytoplasm, accounting for their post-translational regulation. Rescue assay demonstrated that miR-24-3p exerted its anti-cancer role by suppressing LAMB3 expression. Finally, by using a subcutaneous xenotransplanted tumor model, we demonstrated that miR-24-3p overexpression inhibited the proliferation of PDAC by suppressing LAMB3 expression in vivo. Collectively, our results provide evidence that the miR-24-3p/LAMB3 axis plays a vital role in the progression of PDAC and indicate that the miR-24-3p/LAMB3 axis may represent a novel therapeutic target for PDAC. |
format | Online Article Text |
id | pubmed-6985431 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69854312020-02-07 MiR-24-3p Inhibits the Progression of Pancreatic Ductal Adenocarcinoma Through LAMB3 Downregulation Huang, Wenjie Gu, Jianyou Tao, Tian Zhang, Junfeng Wang, Huaizhi Fan, Yingfang Front Oncol Oncology Pancreatic ductal adenocarcinoma (PDAC) is associated with several genetic syndromes. However, the molecular mechanism underlying PDAC progression is still unknown. In this study, we showed that Laminin Subunit Beta 3 (LAMB3) was aberrantly overexpressed in PDAC and was closely associated with the overall survival rate of patients with PDAC. Functional studies demonstrated that LAMB3 played important roles in cell proliferation, the cell cycle, and invasion capacity. Using bioinformatics analysis, we determined that miR-24-3p was an upstream miRNA of LAMB3, and further experiments verified that miR-24-3p regulated LAMB3 expression in PDAC cells. A dual-luciferase reporter system demonstrated that miR-24-3p directly targeted the LAMB3 3'UTR, and FISH assay confirmed that miR-24-3p and LAMB3 mRNA mostly resided in cytoplasm, accounting for their post-translational regulation. Rescue assay demonstrated that miR-24-3p exerted its anti-cancer role by suppressing LAMB3 expression. Finally, by using a subcutaneous xenotransplanted tumor model, we demonstrated that miR-24-3p overexpression inhibited the proliferation of PDAC by suppressing LAMB3 expression in vivo. Collectively, our results provide evidence that the miR-24-3p/LAMB3 axis plays a vital role in the progression of PDAC and indicate that the miR-24-3p/LAMB3 axis may represent a novel therapeutic target for PDAC. Frontiers Media S.A. 2020-01-21 /pmc/articles/PMC6985431/ /pubmed/32039003 http://dx.doi.org/10.3389/fonc.2019.01499 Text en Copyright © 2020 Huang, Gu, Tao, Zhang, Wang and Fan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Huang, Wenjie Gu, Jianyou Tao, Tian Zhang, Junfeng Wang, Huaizhi Fan, Yingfang MiR-24-3p Inhibits the Progression of Pancreatic Ductal Adenocarcinoma Through LAMB3 Downregulation |
title | MiR-24-3p Inhibits the Progression of Pancreatic Ductal Adenocarcinoma Through LAMB3 Downregulation |
title_full | MiR-24-3p Inhibits the Progression of Pancreatic Ductal Adenocarcinoma Through LAMB3 Downregulation |
title_fullStr | MiR-24-3p Inhibits the Progression of Pancreatic Ductal Adenocarcinoma Through LAMB3 Downregulation |
title_full_unstemmed | MiR-24-3p Inhibits the Progression of Pancreatic Ductal Adenocarcinoma Through LAMB3 Downregulation |
title_short | MiR-24-3p Inhibits the Progression of Pancreatic Ductal Adenocarcinoma Through LAMB3 Downregulation |
title_sort | mir-24-3p inhibits the progression of pancreatic ductal adenocarcinoma through lamb3 downregulation |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985431/ https://www.ncbi.nlm.nih.gov/pubmed/32039003 http://dx.doi.org/10.3389/fonc.2019.01499 |
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