TY - JOUR
T1 - Potential of tumor-suppressive miR-596 targeting LGALS3BP as a therapeutic agent in oral cancer
AU - Endo, Hironori
AU - Muramatsu, Tomoki
AU - Furuta, Mayuko
AU - Uzawa, Narikazu
AU - Pimkhaokham, Atiphan
AU - Amagasa, Teruo
AU - Inazawa, Johji
AU - Kozaki, Ken ichi
N1 - Funding Information:
Grant-in-Aid for Scientific Research (A 22240090), (B 23390077), and (C 20592136), and Scientific Research on Priority Areas and Innovative Areas, and a Global Center of Excellence (GCOE) Program for International Research Center for Molecular Science in Tooth and Bone Diseases from the Ministry of Education, Culture, Sports, Science, and Technology, Japan; Health and Labour Sciences Research Grant by the Ministry of Health, Labour and Welfare, Japan; New Energy and Industrial Technology Development Organization (NEDO 22134002).
PY - 2013/3
Y1 - 2013/3
N2 - 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.
AB - 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.
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U2 - 10.1093/carcin/bgs376
DO - 10.1093/carcin/bgs376
M3 - Article
C2 - 23233740
AN - SCOPUS:84874766051
VL - 34
SP - 560
EP - 569
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 3
ER -