Tumor suppressive microRNA-375 regulates lactate dehydrogenase B in maxillary sinus squamous cell carcinoma

Int J Oncol. 2012 Jan;40(1):185-93. doi: 10.3892/ijo.2011.1196. Epub 2011 Sep 12.


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 dehydro-genase 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Base Sequence
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / therapy
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics
  • L-Lactate Dehydrogenase / antagonists & inhibitors
  • L-Lactate Dehydrogenase / biosynthesis
  • L-Lactate Dehydrogenase / genetics*
  • Male
  • Maxillary Sinus Neoplasms / enzymology
  • Maxillary Sinus Neoplasms / genetics*
  • Maxillary Sinus Neoplasms / therapy
  • MicroRNAs / administration & dosage
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Middle Aged
  • Molecular Sequence Data
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Transfection


  • Isoenzymes
  • MIRN375 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • L-Lactate Dehydrogenase
  • lactate dehydrogenase 1