Potential of tumor-suppressive miR-596 targeting LGALS3BP as a therapeutic agent in oral cancer

Hironori Endo, Tomoki Muramatsu, Mayuko Furuta, Narikazu Uzawa, Atiphan Pimkhaokham, Teruo Amagasa, Johji Inazawa, Ken ichi Kozaki

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42 Citations (Scopus)

Abstract

The incidence and mortality statistics for oral squamous cell carcinoma (OSCC) were 10th and 12th, respectively, in human cancers diagnosed worldwide in 2008. In this study, to identify novel tumor-suppressive microRNAs (TS-miRNAs) and their direct targets in OSCC, we performed methylation-based screening for 43 miRNAs encoded by 46 miRNA genes located within 500bp downstream of 40 CpG islands and genome-wide gene expression profiling in combination with a prediction database analysis, respectively, in 18 cell lines, resulting in the identification of a novel TS-miRNA miR-596 directly targeting LGALS3BP/Mac-2 BP/90K. DNA hypermethylation of CpG island located 5'-upstream of miR-596 gene was frequently observed in OSCC cell lines (100% of 18 cell lines) and primary OSCC cases (46.2 and 76.3% of 26 Japanese and 38 Thais primary cases, respectively) in a tumor-specific manner. The ectopic transfection of double-stranded RNA (dsRNA) mimicking miR-596 or specific small interfering RNA for LGALS3BP significantly induced growth inhibition and apoptosis in cell lines lacking miR-596 expression or overexpressing LGALS3BP, respectively, in a manner associated with a suppression of ERK1/2 phosphorylation. Moreover, we also mention the effect of dsRNA mimicking miR-596 on the growth of an OSCC cell line in vivo. Our findings define a central role for miR-596 in OSCC and suggest the potential of miR-596 as an anticancer agent for miRNA replacement therapy in OSCC.

Original languageEnglish
Pages (from-to)560-569
Number of pages10
JournalCarcinogenesis
Volume34
Issue number3
DOIs
Publication statusPublished - Mar 1 2013

ASJC Scopus subject areas

  • Cancer Research

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    Endo, H., Muramatsu, T., Furuta, M., Uzawa, N., Pimkhaokham, A., Amagasa, T., Inazawa, J., & Kozaki, K. I. (2013). Potential of tumor-suppressive miR-596 targeting LGALS3BP as a therapeutic agent in oral cancer. Carcinogenesis, 34(3), 560-569. https://doi.org/10.1093/carcin/bgs376