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Biochim Biophys Acta. 2016 Oct;1862(10):1926-37. doi: 10.1016/j.bbadis.2016.07.017. Epub 2016 Jul 28.

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.

Author information

1
Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Nowon-gil 75, Nowon-gu, Seoul 139-706, Republic of Korea; Laboratory of Biochemistry, School of Life Sciences and Biotechnology, Korea University, Anam-ro 145, Seongbuk-gu, Seoul 136-701, Republic of Korea.
2
Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Nowon-gil 75, Nowon-gu, Seoul 139-706, Republic of Korea.
3
Department of Pathology, Yonsei University Wonju College of Medicine, Ilsan-dong 162, Wonju, Kangwon-do 220-701, Republic of Korea.
4
Laboratory of Biochemistry, School of Life Sciences and Biotechnology, Korea University, Anam-ro 145, Seongbuk-gu, Seoul 136-701, Republic of Korea.
5
Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Nowon-gil 75, Nowon-gu, Seoul 139-706, Republic of Korea. Electronic address: yhhan@kirams.re.kr.

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 miR-5582-5p 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.

KEYWORDS:

CDK2; GAB1; MicroRNA; SHC1; Tumor suppressor; miR-5582-5p

PMID:
27475256
DOI:
10.1016/j.bbadis.2016.07.017
[Indexed for MEDLINE]
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