miR-204-5p inhibits proliferation and invasion and enhances chemotherapeutic sensitivity of colorectal cancer cells by downregulating RAB22A

miR-204-5p was found to be downregulated in colorectal cancer tissues in our preliminary microarray analyses. However, the function of miR-204-5p in colorectal cancer remains unknown. We therefore investigated the role, mechanism, and clinical significance of miR-204-5p in colorectal cancer developm...

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Published in:Clinical cancer research Vol. 20; no. 23; p. 6187
Main Authors: Yin, Yuan, Zhang, Binbin, Wang, Weili, Fei, Bojian, Quan, Chao, Zhang, Jiwei, Song, Mingxu, Bian, Zehua, Wang, Qifeng, Ni, Shujuan, Hu, Yaling, Mao, Yong, Zhou, Leyuan, Wang, Yugang, Yu, Jian, Du, Xiang, Hua, Dong, Huang, Zhaohui
Format: Journal Article
Language:English
Published: United States 01.12.2014
Subjects:
Animals
Base Sequence
Binding Sites
Cell Line, Tumor
Cell Movement - genetics
Cell Proliferation
Cell Transformation, Neoplastic - genetics
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - genetics
Colorectal Neoplasms - mortality
Colorectal Neoplasms - pathology
Disease Models, Animal
DNA Methylation
Down-Regulation
Drug Resistance, Neoplasm - genetics
Gene Expression Regulation, Neoplastic
Humans
Male
Mice
MicroRNAs - chemistry
MicroRNAs - genetics
Prognosis
Promoter Regions, Genetic
rab GTP-Binding Proteins - chemistry
rab GTP-Binding Proteins - genetics
RNA Interference
Tumor Burden
Xenograft Model Antitumor Assays
ISSN:1078-0432, 1557-3265, 1557-3265
Online Access:Get more information
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Summary:miR-204-5p was found to be downregulated in colorectal cancer tissues in our preliminary microarray analyses. However, the function of miR-204-5p in colorectal cancer remains unknown. We therefore investigated the role, mechanism, and clinical significance of miR-204-5p in colorectal cancer development and progression. We measured the expression of miR-204-5p and determined its correlation with patient prognoses. Ectopic expression in colorectal cancer cells, xenografts, and pulmonary metastasis models was used to evaluate the effects of miR-204-5p on proliferation, migration, and chemotherapy sensitivity. Luciferase assay and Western blotting were performed to validate the potential targets of miR-204-5p after the preliminary screening by a microarray analysis and computer-aided algorithms. miR-204-5p is frequently downregulated in colorectal cancer tissues, and survival analysis showed that the downregulation of miR-204-5p in colorectal cancer was associated with poor prognoses. Ectopic miR-204-5p expression repressed colorectal cancer cell growth both in vitro and in vivo. Moreover, restoring miR-204-5p expression inhibited colorectal cancer migration and invasion and promoted tumor sensitivity to chemotherapy. Mechanistic investigations revealed that RAB22A, a member of the RAS oncogene family, is a direct functional target of miR-204-5p in colorectal cancer. Furthermore, RAB22A protein levels in colorectal cancer tissues were frequently increased and negatively associated with miR-204-5p levels and survival time. Our results demonstrate for the first time that miR-204-5p acts as a tumor suppressor in colorectal cancer through inhibiting RAB22A and reveal RAB22A to be a new oncogene and prognostic factor for colorectal cancer.
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ISSN:1078-0432
1557-3265
1557-3265
DOI:10.1158/1078-0432.CCR-14-1030