Aberrant DNA hypomethylation of miR-196b contributes to migration and invasion of oral cancer.
MicroRNAs (miRs) are a class of small endogenous non-coding RNAs of ~21-24 nucleotides in length. Previous studies have indicated that miR-196b has either an oncogenic or tumor-suppressive function in various types of cancer. However, the biological role of miR-196b in oral squamous cell carcinoma (OSCC) remains unclear. In the present study, the expression levels of miR-196b were examined in oral cancer tissues and corresponding adjacent normal tissues from 69 OSCC patients using stem-loop reverse transcription-quantitative polymerase chain reaction. The results indicated that miR-196b was significantly overexpressed in OSCC tissues compared with the corresponding adjacent normal tissue samples (64 of 69, 92.7%, P<0.001). Analysis of the methylation status of the miR-196b gene indicated more frequent hypomethylation of the CpG islands located upstream of the miR-196b gene in the OSCC tissues than in the adjacent normal tissues (32 of 69, 46.3%), and the methylation status of miR-196b correlated inversely with its expression levels. Furthermore, the unmethylated status of the miR-196b promoter correlated with poor disease-specific survival in OSCC patients (P=0.035). Functional analysis revealed that ectopic miR-196b expression promoted oral cancer cell migration and invasion abilities, and that silencing of miR-196b could abrogatein vitromigration and invasion of oral cancer cells. Collectively, the present findings indicate that the epigenetic regulation of miR-196b expression plays a crucial role in modulating cell migration and invasion during OSCC progression, and thus may serve as a potential prognosis marker or therapeutic target for OSCC.
Department of Otolaryngology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, R.O.C.; Department of Nursing, Yuh-Ing Junior College of Health Care and Management, Kaohsiung 807, Taiwan, R.O.C.
Yu-Yi
YY
Hou
Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan, R.O.C.; Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, R.O.C.
Jyun-Jie
JJ
You
Department of Stomatology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, R.O.C.; Department of Dental Technology, Shu-Zen Junior College of Medicine and Management, Kaohsiung 821, Taiwan, R.O.C.
Cheng-Mei
CM
Yang
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, R.O.C.
Hung-Wei
HW
Pan
Department of Stomatology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, R.O.C.; Department of Dental Technology, Shu-Zen Junior College of Medicine and Management, Kaohsiung 821, Taiwan, R.O.C.
Hung-Chih
HC
Chen
Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, R.O.C.
Jang-Hwa
JH
Lee
Department of Otolaryngology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, R.O.C.
Yaoh-Shiang
YS
Lin
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, R.O.C.
Huei-Han
HH
Liou
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, R.O.C.
Pei-Feng
PF
Liu
Department of Otolaryngology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, R.O.C.
Chao-Chuan
CC
Chi
Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan, R.O.C.; Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, R.O.C.
Luo-Ping
LP
Ger
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, R.O.C.
Kuo-Wang
KW
Tsai
DNA methylation; microRNA; migration; oral cancer