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

Hyun Ju An, Seo Young Kwak, Je Ok Yoo, Jae Sung Kim, In Hwa Bae, Myung Jin Park, Mee Yon Cho, Joon Kim, Young Hoon Han

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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.

Original languageEnglish
Pages (from-to)1926-1937
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1862
Issue number10
DOIs
Publication statusPublished - 2016 Oct 1

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All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology

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