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miR-491-5p functions as a tumor suppressor by targeting IGF2 in colorectal cancer

BACKGROUND: Dysregulation of miRNAs is critically implicated in tumorigenesis, and aberrant expression of miR-491-5p has been reported to play a key role in initiation and progression of various cancers. However, the biological function and underlying mechanism of miR-491-5p in colorectal cancer (CR...

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Autores principales: Lu, Lei, Cai, Ming, Peng, Meixia, Wang, Fei, Zhai, Xiaofeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391127/
https://www.ncbi.nlm.nih.gov/pubmed/30863186
http://dx.doi.org/10.2147/CMAR.S183085
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author Lu, Lei
Cai, Ming
Peng, Meixia
Wang, Fei
Zhai, Xiaofeng
author_facet Lu, Lei
Cai, Ming
Peng, Meixia
Wang, Fei
Zhai, Xiaofeng
author_sort Lu, Lei
collection PubMed
description BACKGROUND: Dysregulation of miRNAs is critically implicated in tumorigenesis, and aberrant expression of miR-491-5p has been reported to play a key role in initiation and progression of various cancers. However, the biological function and underlying mechanism of miR-491-5p in colorectal cancer (CRC) remain elusive. METHODS: Quantitative real-time PCR (qRT-PCR) was employed to evaluate the levels of miR-491-5p and IGF2 mRNA expression in CRC tissues, cell lines and plasma. Cell counting kit-8 and colony formation assays were used to detect the effects of miR-491-5p on CRC cell growth. Luciferase reporter assays were applied to confirm the miR-491-5p target gene. In vivo experiments were conducted in nude mice. RESULTS: miR-491-5p was found to be obviously downregulated in CRC tissues and cell lines, and decreased miR-491-5p expression level was shown to be associated with differentiation, TNM stage and poor overall survival (OS). miR-491-5p overexpression suppressed CRC cell proliferation both in vitro and in vivo. Mechanically, insulin-like growth factor 2 (IGF2) was identified to be a direct target of miR-491-5p in CRC cells, and overexpression of IGF2 rescued the miR-491-5p-induced suppression of proliferation in CRC cells. Finally, we demonstrated that plasma miR-491-5p expression was decreased in CRC when compared to healthy controls and might be an effective diagnostic biomarker for CRC. CONCLUSION: These data showed that miR-491-5p functioned as a tumor suppressor by targeting IGF2 in CRC, and miR-491-5p could serve as a potential diagnostic and prognostic biomarker for CRC.
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spelling pubmed-63911272019-03-12 miR-491-5p functions as a tumor suppressor by targeting IGF2 in colorectal cancer Lu, Lei Cai, Ming Peng, Meixia Wang, Fei Zhai, Xiaofeng Cancer Manag Res Original Research BACKGROUND: Dysregulation of miRNAs is critically implicated in tumorigenesis, and aberrant expression of miR-491-5p has been reported to play a key role in initiation and progression of various cancers. However, the biological function and underlying mechanism of miR-491-5p in colorectal cancer (CRC) remain elusive. METHODS: Quantitative real-time PCR (qRT-PCR) was employed to evaluate the levels of miR-491-5p and IGF2 mRNA expression in CRC tissues, cell lines and plasma. Cell counting kit-8 and colony formation assays were used to detect the effects of miR-491-5p on CRC cell growth. Luciferase reporter assays were applied to confirm the miR-491-5p target gene. In vivo experiments were conducted in nude mice. RESULTS: miR-491-5p was found to be obviously downregulated in CRC tissues and cell lines, and decreased miR-491-5p expression level was shown to be associated with differentiation, TNM stage and poor overall survival (OS). miR-491-5p overexpression suppressed CRC cell proliferation both in vitro and in vivo. Mechanically, insulin-like growth factor 2 (IGF2) was identified to be a direct target of miR-491-5p in CRC cells, and overexpression of IGF2 rescued the miR-491-5p-induced suppression of proliferation in CRC cells. Finally, we demonstrated that plasma miR-491-5p expression was decreased in CRC when compared to healthy controls and might be an effective diagnostic biomarker for CRC. CONCLUSION: These data showed that miR-491-5p functioned as a tumor suppressor by targeting IGF2 in CRC, and miR-491-5p could serve as a potential diagnostic and prognostic biomarker for CRC. Dove Medical Press 2019-02-22 /pmc/articles/PMC6391127/ /pubmed/30863186 http://dx.doi.org/10.2147/CMAR.S183085 Text en © 2019 Lu 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
Lu, Lei
Cai, Ming
Peng, Meixia
Wang, Fei
Zhai, Xiaofeng
miR-491-5p functions as a tumor suppressor by targeting IGF2 in colorectal cancer
title miR-491-5p functions as a tumor suppressor by targeting IGF2 in colorectal cancer
title_full miR-491-5p functions as a tumor suppressor by targeting IGF2 in colorectal cancer
title_fullStr miR-491-5p functions as a tumor suppressor by targeting IGF2 in colorectal cancer
title_full_unstemmed miR-491-5p functions as a tumor suppressor by targeting IGF2 in colorectal cancer
title_short miR-491-5p functions as a tumor suppressor by targeting IGF2 in colorectal cancer
title_sort mir-491-5p functions as a tumor suppressor by targeting igf2 in colorectal cancer
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391127/
https://www.ncbi.nlm.nih.gov/pubmed/30863186
http://dx.doi.org/10.2147/CMAR.S183085
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