MicroRNA-23a/27a/24-2 cluster promotes gastric cancer cell proliferation synergistically

Kate Hua; Yu-Ting Chen; Chian-Feng Chen; Ya-Syuan Tang; Tzu-Ting Huang; Yu-Cheng Lin; Tien-Shun Yeh; Kuo-Hung Huang; Hsin-Chen Lee; Ming-Ta Hsu; Chin-Wen Chi; Chew-Wun Wu; Chi-Hung Lin; Yueh-Hsin Ping

doi:10.3892/ol.2018.8924

MicroRNA-23a/27a/24-2 cluster promotes gastric cancer cell proliferation synergistically

Oncol Lett. 2018 Aug;16(2):2319-2325. doi: 10.3892/ol.2018.8924. Epub 2018 Jun 7.

Authors

Kate Hua^{1

2}, Yu-Ting Chen¹, Chian-Feng Chen², Ya-Syuan Tang¹, Tzu-Ting Huang^{1

3}, Yu-Cheng Lin¹, Tien-Shun Yeh^{1

3

4

5}, Kuo-Hung Huang^{6

7}, Hsin-Chen Lee¹, Ming-Ta Hsu^{2

4}, Chin-Wen Chi^{1

8}, Chew-Wun Wu⁶, Chi-Hung Lin^{2

9

10}, Yueh-Hsin Ping^{1

2

10}

Affiliations

¹ Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan, R.O.C.
² VYM Genome Research Center, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan, R.O.C.
³ Department of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan, R.O.C.
⁴ Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 11221, Taiwan, R.O.C.
⁵ Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.
⁶ Department of Surgery, Taipei Veterans General Hospital, Taipei 11221, Taiwan, R.O.C.
⁷ Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan, R.O.C.
⁸ Department of Medical Research, Taipei Veterans General Hospital, Taipei 11221, Taiwan, R.O.C.
⁹ Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 11221, Taiwan, R.O.C.
¹⁰ Institute of Biophotonics, National Yang-Ming University, Taipei 11221, Taiwan, R.O.C.

Abstract

Previous studies have indicated that certain microRNAs (miRNAs/miRs) function as either tumor suppressors or oncogenes in human cancer. The present study identified the miR-23a/27a/24-2 cluster, containing miR-23, miR-27a and miR-24, as an oncogene in gastric cancer. The expression of the miR-23a/27a/24-2 cluster was upregulated in clinical gastric cancer tissues. Transfection with inhibitors of miR-23a, miR-27a, or miR-24, either independently or together, repressed in vitro colony formation and in vivo tumor formation. The miR23a/27a/24-2 cluster inhibitors repressed the growth of gastric cancer cells in a synergistic manner. In addition, treatment with lower doses of the miRNA inhibitor mixture induced the formation of apoptotic bodies. According to computational predictions using TargetScan, suppressor of cytokine-induced signaling 6 (SOCS6) was identified as one of the downstream target genes of the miR-23a/27a/24-2 cluster. The expression of SOCS6 was significantly lower in tumor tissues than in matched normal tissues (P<0.01) and was associated with poor survival (P<0.00001). Taken together, these results strongly suggested that the miR-23a/27a/24-2 cluster may mediate the progression of gastric cancer through the suppression of SOCS6 expression. The present study also provides a novel molecular target for the development of an anti-gastric cancer agent.

Keywords: gastric cancer; microRNA-23a/27a/24-2 cluster; suppressor of cytokine-induced signaling 6.