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Novel miR-5582-5p functions as a tumor suppressor by inducing apoptosis and cell cycle arrest in cancer cells through direct targeting of GAB1, SHC1, and CDK2

Authors
An, Hyun-JuKwak, Seo-YoungYoo, Je-OkKim, Jae-SungBae, In-HwaPark, Myung-JinCho, Mee-YonKim, JoonHan, Young-Hoon
Issue Date
10월-2016
Publisher
ELSEVIER
Keywords
MicroRNA; miR-5582-5p; Tumor suppressor; GABI; SHC1; CDK2
Citation
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v.1862, no.10, pp.1926 - 1937
Indexed
SCIE
SCOPUS
Journal Title
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume
1862
Number
10
Start Page
1926
End Page
1937
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/87356
DOI
10.1016/j.bbadis.2016.07.017
ISSN
0925-4439
Abstract
MicroRNAs (miRNAs) play pivotal roles in tumorigenesis as either tumor suppressors or oncogenes. In the present study, we discovered and demonstrated the tumor suppressive function of a novel miRNA miR-5582-5p. miR-5582-5p induced apoptosis and cell cycle arrest in cancer cells, but not in normal cells. GAB1, SHC1, and CDK2 were identified as direct targets of miR-5582-5p. Knockdown of GAB1/SHC1 or CDK2 phenocopied the apoptotic or cell cycle arrest-inducing function of miR-5582-5p, respectively. The expression of miR-5582-5p was lower in tumor tissues than in adjacent normal tissues of colorectal cancer patients, while the expression of the target proteins exhibited patterns opposite to that of miR-5582-5p. Intratumoral injection of a miR5582-5p mimic or induced expression of miR-5582-5p in tumor cells suppressed tumor growth in HCT116 xenografts. Collectively, our results suggest a novel tumor suppressive function for miR-5582-5p and its potential applicability for tumor control. (C) 2016 Elsevier B.V. All rights reserved.
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