title: 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.
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.
authors.affiliation: 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.
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: An
authors.affiliation: 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.
authors.forename: Seo-Young
authors.initials: SY
authors.lastname: Kwak
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Nowon-gil 75, Nowon-gu, Seoul 139-706, Republic of Korea.
authors.forename: Je-Ok
authors.initials: JO
authors.lastname: Yoo
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Nowon-gil 75, Nowon-gu, Seoul 139-706, Republic of Korea.
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Nowon-gil 75, Nowon-gu, Seoul 139-706, Republic of Korea.
authors.forename: In-Hwa
authors.initials: IH
authors.lastname: Bae
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Nowon-gil 75, Nowon-gu, Seoul 139-706, Republic of Korea.
authors.forename: Myung-Jin
authors.initials: MJ
authors.lastname: Park
authors.affiliation: Department of Pathology, Yonsei University Wonju College of Medicine, Ilsan-dong 162, Wonju, Kangwon-do 220-701, Republic of Korea.
authors.forename: Mee-Yon
authors.initials: MY
authors.lastname: Cho
authors.affiliation: Laboratory of Biochemistry, School of Life Sciences and Biotechnology, Korea University, Anam-ro 145, Seongbuk-gu, Seoul 136-701, Republic of Korea.
authors.forename: Joon
authors.initials: J
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Han
mesh_terms: D000072283:A549 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D017209:Apoptosis; D059447:Cell Cycle Checkpoints; D051357:Cyclin-Dependent Kinase 2 / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D045325:HCT116 Cells; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C098587:GAB1 protein, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C528024:SHC1 protein, human; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2
keywords: CDK2; GAB1; MicroRNA; SHC1; Tumor suppressor; miR-5582-5p