MicroRNA-494 promotes cancer progression and targets adenomatous polyposis coli in colorectal cancer

Abstract Background Aberrant activation of the Wnt/β-catenin signaling pathway is frequently observed in colorectal cancer (CRC). β-catenin is the major Wnt signaling pathway effector and inactivation of adenomatous polyposis coli (APC) results in nuclear accumulation of β-catenin. It has been sugge...

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Main Authors: Ying Zhang, Lu Guo, Yuhuan Li, Gui-Hai Feng, Fei Teng, Wei Li, Qi Zhou
Format: Article
Language:English
Published: BMC 2018-01-01
Series:Molecular Cancer
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12943-017-0753-1
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author Ying Zhang
Lu Guo
Yuhuan Li
Gui-Hai Feng
Fei Teng
Wei Li
Qi Zhou
author_facet Ying Zhang
Lu Guo
Yuhuan Li
Gui-Hai Feng
Fei Teng
Wei Li
Qi Zhou
author_sort Ying Zhang
collection DOAJ
description Abstract Background Aberrant activation of the Wnt/β-catenin signaling pathway is frequently observed in colorectal cancer (CRC). β-catenin is the major Wnt signaling pathway effector and inactivation of adenomatous polyposis coli (APC) results in nuclear accumulation of β-catenin. It has been suggested that inactivation of APC plays an important role in activation of the Wnt/β-catenin pathway and in the progression of colorectal tumorigenesis. However, the mechanism through which APC mediates colorectal tumorigenesis is not understood. Increasing evidence suggests that the dysregulation of microRNAs (miRNAs) is involved in colorectal tumorigenesis. Although miR-494 has been reported as being an upregulated miRNA, the interplay between miR-494 and APC-mediated colorectal tumorigenesis progression remains unclear. Methods The expression of miR-494 in tissues from patients diagnosed with CRC was analyzed using a microarray and real-time PCR. The effects of miR-494 on cell proliferation and tumorigenesis in CRC cells were analyzed by flow cytometry, colony formation assays, BrdU incorporation assays, and CCK8 assays. The correlation between miR-494 expression and APC expression, as well as the mechanisms by which miR-494 regulates APC in CRC were also addressed. Results miR-494 was significantly upregulated in CRC tissues, and this increase was negatively associated with APC expression. APC was confirmed to be a direct target of miR-494 in CRC. Furthermore, overexpression of miR-494 induced Wnt/β-catenin signaling by targeting APC, thus promoting CRC cell growth. Conclusions This study provides novel insights into the role of miR-494 in controlling CRC cell proliferation and tumorigenesis, and identifies miR-494 as a potential prognostic marker and therapeutic target.
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spelling doaj.art-f9ae56d34daf40d7918e42f9a6ba14162022-12-22T00:12:35ZengBMCMolecular Cancer1476-45982018-01-0117111110.1186/s12943-017-0753-1MicroRNA-494 promotes cancer progression and targets adenomatous polyposis coli in colorectal cancerYing Zhang0Lu Guo1Yuhuan Li2Gui-Hai Feng3Fei Teng4Wei Li5Qi Zhou6State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesAbstract Background Aberrant activation of the Wnt/β-catenin signaling pathway is frequently observed in colorectal cancer (CRC). β-catenin is the major Wnt signaling pathway effector and inactivation of adenomatous polyposis coli (APC) results in nuclear accumulation of β-catenin. It has been suggested that inactivation of APC plays an important role in activation of the Wnt/β-catenin pathway and in the progression of colorectal tumorigenesis. However, the mechanism through which APC mediates colorectal tumorigenesis is not understood. Increasing evidence suggests that the dysregulation of microRNAs (miRNAs) is involved in colorectal tumorigenesis. Although miR-494 has been reported as being an upregulated miRNA, the interplay between miR-494 and APC-mediated colorectal tumorigenesis progression remains unclear. Methods The expression of miR-494 in tissues from patients diagnosed with CRC was analyzed using a microarray and real-time PCR. The effects of miR-494 on cell proliferation and tumorigenesis in CRC cells were analyzed by flow cytometry, colony formation assays, BrdU incorporation assays, and CCK8 assays. The correlation between miR-494 expression and APC expression, as well as the mechanisms by which miR-494 regulates APC in CRC were also addressed. Results miR-494 was significantly upregulated in CRC tissues, and this increase was negatively associated with APC expression. APC was confirmed to be a direct target of miR-494 in CRC. Furthermore, overexpression of miR-494 induced Wnt/β-catenin signaling by targeting APC, thus promoting CRC cell growth. Conclusions This study provides novel insights into the role of miR-494 in controlling CRC cell proliferation and tumorigenesis, and identifies miR-494 as a potential prognostic marker and therapeutic target.http://link.springer.com/article/10.1186/s12943-017-0753-1Colorectal cancermicroRNAmiR-494Apc
spellingShingle Ying Zhang
Lu Guo
Yuhuan Li
Gui-Hai Feng
Fei Teng
Wei Li
Qi Zhou
MicroRNA-494 promotes cancer progression and targets adenomatous polyposis coli in colorectal cancer
Molecular Cancer
Colorectal cancer
microRNA
miR-494
Apc
title MicroRNA-494 promotes cancer progression and targets adenomatous polyposis coli in colorectal cancer
title_full MicroRNA-494 promotes cancer progression and targets adenomatous polyposis coli in colorectal cancer
title_fullStr MicroRNA-494 promotes cancer progression and targets adenomatous polyposis coli in colorectal cancer
title_full_unstemmed MicroRNA-494 promotes cancer progression and targets adenomatous polyposis coli in colorectal cancer
title_short MicroRNA-494 promotes cancer progression and targets adenomatous polyposis coli in colorectal cancer
title_sort microrna 494 promotes cancer progression and targets adenomatous polyposis coli in colorectal cancer
topic Colorectal cancer
microRNA
miR-494
Apc
url http://link.springer.com/article/10.1186/s12943-017-0753-1
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