Tumor suppressive microRNA-375 regulates lactate dehydrogenase B in maxillary sinus squamous cell carcinoma
- Authors: Takashi Kinoshita, Nijiro Nohata, Hirofumi Yoshino, Toyoyuki Hanazawa, Naoko Kikkawa, Lisa Fujimura, Takeshi Chiyomaru, Kazumori Kawakami, Hideki Enokida, Masayuki Nakagawa, Yoshitaka Okamoto, Naohiko Seki
Published online on: Monday, September 12, 2011
- Pages: 185-193
- DOI: 10.3892/ijo.2011.1196
The expression of microRNA-375 (miR-375) is significantly reduced in cancer tissues of maxillary sinus squamous cell carcinoma (MSSCC). The aim of this study was to investigate the functional significance of miR-375 and a possible regulatory role in the MSSCC networks. Restoration of miR-375 significantly inhibited cancer cell proliferation and invasion in IMC-3 cells, suggesting that miR-375 functions as a tumor suppressor in MSSCC. Genome-wide gene expression data and luciferase reporter assays indicated that lactate dehydrogenase B (LDHB) was directly regulated by miR-375. Cancer cell proliferation and invasion were significantly inhibited by transfection of si-LDHB into IMC-3 cells, suggesting that LDHB may play a role in MSSCC oncogenic function. In clinical MSSCC specimens, LDHB mRNA levels were up-regulated in cancer tissues, which were inversely correlated with the expression of miR-375. In addition, Kaplan-Meier curves and log-rank tests revealed that the high mRNA expression levels of LDHB had a significant adverse effect on survival rate. The identification of a cancer network regulated by the miR-375 tumor suppressor could provide new insights into the molecular mechanisms of MSSCC oncogenesis.