Cargando…

MicroRNA-940 Targets INPP4A or GSK3β and Activates the Wnt/β-Catenin Pathway to Regulate the Malignant Behavior of Bladder Cancer Cells

In this report, we aimed to explore the role and regulatory mechanism of microRNA-940 (miR-940) in bladder cancer development. The expressions of miR-940 in bladder cancer tissues and cells were measured. miR-940 mimics, miR-940 inhibitor small interference RNA against INPP4A (si-INPP4A), and GSK3β...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Rong, Wu, Yunfeng, Huang, Weihua, Chen, Weijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cognizant Communication Corporation 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844674/
https://www.ncbi.nlm.nih.gov/pubmed/28337959
http://dx.doi.org/10.3727/096504017X14902261600566
_version_ 1783644398145241088
author Wang, Rong
Wu, Yunfeng
Huang, Weihua
Chen, Weijun
author_facet Wang, Rong
Wu, Yunfeng
Huang, Weihua
Chen, Weijun
author_sort Wang, Rong
collection PubMed
description In this report, we aimed to explore the role and regulatory mechanism of microRNA-940 (miR-940) in bladder cancer development. The expressions of miR-940 in bladder cancer tissues and cells were measured. miR-940 mimics, miR-940 inhibitor small interference RNA against INPP4A (si-INPP4A), and GSK3β (si-GSK3β) and their corresponding controls were then transfected into cells. We investigated the effects of miR-940, INPP4A, or GSK3β on cell proliferation, migration, invasion, and apoptosis. Additionally, target prediction and luciferase reporter assays were performed to investigate the targets of miR-940. The regulatory relationship between miR-940 and the Wnt/β-catenin pathway was also investigated. miR-940 was upregulated in bladder cancer tissues and cells. Overexpression of miR-940 significantly increased bladder cancer cell proliferation, promoted migration and invasion, and inhibited cell apoptosis. INPP4A and GSK3β were the direct targets of miR-940, and knockdown of INPP4A or GSK3β significantly increased cancer cell proliferation, migration, and invasion and inhibited cell apoptosis. After miR-940 overexpression, the protein expression levels of c-Myc, cyclin D1, and β-catenin were significantly increased, and the expression levels of p27 and p-β-catenin were markedly decreased. The opposite effects were obtained after suppression of miR-940. XAV939, a tankyrase 1 inhibitor that could inhibit Wnt/β-catenin signaling, significantly reversed the effects of miR-940 overexpression on cell migration and invasion. Our results indicate that overexpression of miR-940 may promote bladder cancer cell proliferation, migration, and invasion and inhibit cell apoptosis via targeting INPP4A or GSK3β and activating the Wnt/β-catenin pathway. Our findings imply the key roles of suppressing miRNA-940 in the therapy of bladder cancer.
format Online
Article
Text
id pubmed-7844674
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Cognizant Communication Corporation
record_format MEDLINE/PubMed
spelling pubmed-78446742021-02-16 MicroRNA-940 Targets INPP4A or GSK3β and Activates the Wnt/β-Catenin Pathway to Regulate the Malignant Behavior of Bladder Cancer Cells Wang, Rong Wu, Yunfeng Huang, Weihua Chen, Weijun Oncol Res Article In this report, we aimed to explore the role and regulatory mechanism of microRNA-940 (miR-940) in bladder cancer development. The expressions of miR-940 in bladder cancer tissues and cells were measured. miR-940 mimics, miR-940 inhibitor small interference RNA against INPP4A (si-INPP4A), and GSK3β (si-GSK3β) and their corresponding controls were then transfected into cells. We investigated the effects of miR-940, INPP4A, or GSK3β on cell proliferation, migration, invasion, and apoptosis. Additionally, target prediction and luciferase reporter assays were performed to investigate the targets of miR-940. The regulatory relationship between miR-940 and the Wnt/β-catenin pathway was also investigated. miR-940 was upregulated in bladder cancer tissues and cells. Overexpression of miR-940 significantly increased bladder cancer cell proliferation, promoted migration and invasion, and inhibited cell apoptosis. INPP4A and GSK3β were the direct targets of miR-940, and knockdown of INPP4A or GSK3β significantly increased cancer cell proliferation, migration, and invasion and inhibited cell apoptosis. After miR-940 overexpression, the protein expression levels of c-Myc, cyclin D1, and β-catenin were significantly increased, and the expression levels of p27 and p-β-catenin were markedly decreased. The opposite effects were obtained after suppression of miR-940. XAV939, a tankyrase 1 inhibitor that could inhibit Wnt/β-catenin signaling, significantly reversed the effects of miR-940 overexpression on cell migration and invasion. Our results indicate that overexpression of miR-940 may promote bladder cancer cell proliferation, migration, and invasion and inhibit cell apoptosis via targeting INPP4A or GSK3β and activating the Wnt/β-catenin pathway. Our findings imply the key roles of suppressing miRNA-940 in the therapy of bladder cancer. Cognizant Communication Corporation 2018-01-19 /pmc/articles/PMC7844674/ /pubmed/28337959 http://dx.doi.org/10.3727/096504017X14902261600566 Text en Copyright © 2018 Cognizant, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives 4.0 International License.
spellingShingle Article
Wang, Rong
Wu, Yunfeng
Huang, Weihua
Chen, Weijun
MicroRNA-940 Targets INPP4A or GSK3β and Activates the Wnt/β-Catenin Pathway to Regulate the Malignant Behavior of Bladder Cancer Cells
title MicroRNA-940 Targets INPP4A or GSK3β and Activates the Wnt/β-Catenin Pathway to Regulate the Malignant Behavior of Bladder Cancer Cells
title_full MicroRNA-940 Targets INPP4A or GSK3β and Activates the Wnt/β-Catenin Pathway to Regulate the Malignant Behavior of Bladder Cancer Cells
title_fullStr MicroRNA-940 Targets INPP4A or GSK3β and Activates the Wnt/β-Catenin Pathway to Regulate the Malignant Behavior of Bladder Cancer Cells
title_full_unstemmed MicroRNA-940 Targets INPP4A or GSK3β and Activates the Wnt/β-Catenin Pathway to Regulate the Malignant Behavior of Bladder Cancer Cells
title_short MicroRNA-940 Targets INPP4A or GSK3β and Activates the Wnt/β-Catenin Pathway to Regulate the Malignant Behavior of Bladder Cancer Cells
title_sort microrna-940 targets inpp4a or gsk3β and activates the wnt/β-catenin pathway to regulate the malignant behavior of bladder cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844674/
https://www.ncbi.nlm.nih.gov/pubmed/28337959
http://dx.doi.org/10.3727/096504017X14902261600566
work_keys_str_mv AT wangrong microrna940targetsinpp4aorgsk3bandactivatesthewntbcateninpathwaytoregulatethemalignantbehaviorofbladdercancercells
AT wuyunfeng microrna940targetsinpp4aorgsk3bandactivatesthewntbcateninpathwaytoregulatethemalignantbehaviorofbladdercancercells
AT huangweihua microrna940targetsinpp4aorgsk3bandactivatesthewntbcateninpathwaytoregulatethemalignantbehaviorofbladdercancercells
AT chenweijun microrna940targetsinpp4aorgsk3bandactivatesthewntbcateninpathwaytoregulatethemalignantbehaviorofbladdercancercells