Cargando…

microRNA-130a is an oncomir suppressing the expression of CRMP4 in gastric cancer

Gastric cancer is one of the most common causes of death worldwide, although its incidence has steadily declined in recent years. There is strong evidence that aberrantly expressed microRNAs (miRNAs) are involved in gastric cancer tumorigenesis. Furthermore, CRMP4 is closely associated with the occu...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhou, Yiran, Li, Ruhong, Yu, Haidong, Wang, Ruotian, Shen, Zhiqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548272/
https://www.ncbi.nlm.nih.gov/pubmed/28831264
http://dx.doi.org/10.2147/OTT.S139443
_version_ 1783255812662099968
author Zhou, Yiran
Li, Ruhong
Yu, Haidong
Wang, Ruotian
Shen, Zhiqiang
author_facet Zhou, Yiran
Li, Ruhong
Yu, Haidong
Wang, Ruotian
Shen, Zhiqiang
author_sort Zhou, Yiran
collection PubMed
description Gastric cancer is one of the most common causes of death worldwide, although its incidence has steadily declined in recent years. There is strong evidence that aberrantly expressed microRNAs (miRNAs) are involved in gastric cancer tumorigenesis. Furthermore, CRMP4 is closely associated with the occurrence and development of gastric cancer, and our predictions suggest that miR-130a, which can promote gastric cancer tumorigenesis, is a potential CRMP4 regulator. In this study, we investigated the expression of CRMP4 and miR-130a in human gastric cancer cell lines by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot (WB) examination and direct interactions between miR-130a and CRMP4 by dual-luciferase reporter assay. We also evaluated the biological roles of miR-130a and CRMP4 in gastric cancer cells by flow cytometry, MTT assay, soft agar colony formation assay, and Transwell tests and confirmed CRMP4 function in vivo, using a tumor xenograft model. Our results demonstrated that CRMP4 expression was significantly decreased at both the gene and protein levels, while miR-130a expression was notably increased, in five human gastric cancer cell lines compared with human gastric epithelial cells. Dual-luciferase reporter assays indicated that CRMP4 was the direct target of miR-130a. Moreover, an inverse regulatory relationship between miR-130a and CRMP4 was verified by qRT-PCR and WB, and overexpression of miR-130a in BGC823 cells enhanced apoptosis and cell proliferation, arrested the cell cycle in G0/G1, and facilitated cell colony formation, invasion, migration, and adhesion, while upregulation of CRMP4 had opposite effects. Finally, the growth and weight of transplanted tumors derived from BGC823 cells in which CRMP4 was knocked down were remarkably reduced. These data indicate that miR-130a is an oncomir targeting CRMP4 and could be developed as a potential prognostic factor and a novel therapeutic target in gastric cancer.
format Online
Article
Text
id pubmed-5548272
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Dove Medical Press
record_format MEDLINE/PubMed
spelling pubmed-55482722017-08-22 microRNA-130a is an oncomir suppressing the expression of CRMP4 in gastric cancer Zhou, Yiran Li, Ruhong Yu, Haidong Wang, Ruotian Shen, Zhiqiang Onco Targets Ther Original Research Gastric cancer is one of the most common causes of death worldwide, although its incidence has steadily declined in recent years. There is strong evidence that aberrantly expressed microRNAs (miRNAs) are involved in gastric cancer tumorigenesis. Furthermore, CRMP4 is closely associated with the occurrence and development of gastric cancer, and our predictions suggest that miR-130a, which can promote gastric cancer tumorigenesis, is a potential CRMP4 regulator. In this study, we investigated the expression of CRMP4 and miR-130a in human gastric cancer cell lines by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot (WB) examination and direct interactions between miR-130a and CRMP4 by dual-luciferase reporter assay. We also evaluated the biological roles of miR-130a and CRMP4 in gastric cancer cells by flow cytometry, MTT assay, soft agar colony formation assay, and Transwell tests and confirmed CRMP4 function in vivo, using a tumor xenograft model. Our results demonstrated that CRMP4 expression was significantly decreased at both the gene and protein levels, while miR-130a expression was notably increased, in five human gastric cancer cell lines compared with human gastric epithelial cells. Dual-luciferase reporter assays indicated that CRMP4 was the direct target of miR-130a. Moreover, an inverse regulatory relationship between miR-130a and CRMP4 was verified by qRT-PCR and WB, and overexpression of miR-130a in BGC823 cells enhanced apoptosis and cell proliferation, arrested the cell cycle in G0/G1, and facilitated cell colony formation, invasion, migration, and adhesion, while upregulation of CRMP4 had opposite effects. Finally, the growth and weight of transplanted tumors derived from BGC823 cells in which CRMP4 was knocked down were remarkably reduced. These data indicate that miR-130a is an oncomir targeting CRMP4 and could be developed as a potential prognostic factor and a novel therapeutic target in gastric cancer. Dove Medical Press 2017-08-03 /pmc/articles/PMC5548272/ /pubmed/28831264 http://dx.doi.org/10.2147/OTT.S139443 Text en © 2017 Zhou et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Zhou, Yiran
Li, Ruhong
Yu, Haidong
Wang, Ruotian
Shen, Zhiqiang
microRNA-130a is an oncomir suppressing the expression of CRMP4 in gastric cancer
title microRNA-130a is an oncomir suppressing the expression of CRMP4 in gastric cancer
title_full microRNA-130a is an oncomir suppressing the expression of CRMP4 in gastric cancer
title_fullStr microRNA-130a is an oncomir suppressing the expression of CRMP4 in gastric cancer
title_full_unstemmed microRNA-130a is an oncomir suppressing the expression of CRMP4 in gastric cancer
title_short microRNA-130a is an oncomir suppressing the expression of CRMP4 in gastric cancer
title_sort microrna-130a is an oncomir suppressing the expression of crmp4 in gastric cancer
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548272/
https://www.ncbi.nlm.nih.gov/pubmed/28831264
http://dx.doi.org/10.2147/OTT.S139443
work_keys_str_mv AT zhouyiran microrna130aisanoncomirsuppressingtheexpressionofcrmp4ingastriccancer
AT liruhong microrna130aisanoncomirsuppressingtheexpressionofcrmp4ingastriccancer
AT yuhaidong microrna130aisanoncomirsuppressingtheexpressionofcrmp4ingastriccancer
AT wangruotian microrna130aisanoncomirsuppressingtheexpressionofcrmp4ingastriccancer
AT shenzhiqiang microrna130aisanoncomirsuppressingtheexpressionofcrmp4ingastriccancer