miR-375 is down-regulated in squamous cervical cancer and inhibits cell migration and invasion via targeting transcription factor SP1

Am J Pathol. 2011 Nov;179(5):2580-8. doi: 10.1016/j.ajpath.2011.07.037. Epub 2011 Sep 21.


Pelvic lymph node metastases are regarded as the most important risk factor and a predictor of poor prognosis for patients with cervical cancer. Exploration of metastasis-related molecules is helpful toward improving the prognosis in cervical cancer. To identify the role of miR-375 in metastasis and progression of cervical cancer, we examined the expression of miR-375 in 170 cervical cancer tissues and 68 normal cervical tissues, using stem-loop quantitative PCR, and found that the expression of miR-375 in cervical cancer tissues was significantly decreased by 4.45-fold, compared with 68 normal tissues. A significant correlation existed between miR-375 expression and clinicopathologic parameters, including lymph node metastasis of cervical cancer. Overexpressed miR-375 suppressed cell proliferation, blocked G1-to-S cell-cycle transition, and inhibited cell migration and invasion in human cervical SiHa and CaSki cells. SP1, a potential target gene of miR-375, was inversely correlated with miR-375 expression in cervical cancer tissues. Moreover, SP1 was negatively regulated by miR-375, and knockdown of SP1 by siRNA inhibited cell malignant behaviors. Thus, our findings suggest that down-regulated miR-375 promotes cell malignant behaviors via the target gene SP1 and may consequently contribute to the progression of cervical cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / metabolism*
  • Cell Movement / genetics
  • Cell Proliferation
  • Down-Regulation
  • Female
  • G1 Phase Cell Cycle Checkpoints / physiology
  • Gene Expression
  • Gene Knockdown Techniques
  • Humans
  • Lymphatic Metastasis
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • RNA, Neoplasm / metabolism
  • Sp1 Transcription Factor / metabolism*
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms / metabolism*


  • Biomarkers, Tumor
  • MIRN375 microRNA, human
  • MicroRNAs
  • RNA, Neoplasm
  • Sp1 Transcription Factor