Suppressed miR-424 expression via upregulation of target gene Chk1 contributes to the progression of cervical cancer

Oncogene. 2013 Feb 21;32(8):976-87. doi: 10.1038/onc.2012.121. Epub 2012 Apr 2.


MicroRNAs (miRNAs) act as important gene regulators in human genomes and their aberrant expression links to many malignancies. We previously identified a different characteristic miRNA expression profile in cervical cancer from that in cervical normal tissues, including the downregulated miR-424. However, the role and mechanism of miR-424 in cervical cancer still remain unknown. Here, we focused on identifying the tumor-suppressive function and clinical significance of miR-424 and exploring the mechanistic relevance by characterizing its target. We showed a significantly decreased expression of miR-424 in 147 cervical cancer tissues versus 74 cervical normal tissues by performing quantitative RT-PCR. In 147 cervical cancer tissue samples, low-level expression of miR-424 was positively correlated with poor tumor differentiation, advanced clinical stage, lymph node metastasis and other poor prognostic clinicopathological parameters. Further in vitro observations showed that enforced expression of miR-424 inhibited cell growth by both enhancing apoptosis and blocking G1/S transition, and suppressed cell migration and invasion in two human cervical cancer cell lines, SiHa and CaSki, implying that miR-424 functions as a tumor suppressor in the progression of cervical cancer. Interestingly, overexpression of miR-424 inhibited the expression of protein checkpoint kinase 1 (Chk1) and phosphorylated Chk1 (p-Chk1) at residues Ser345 and decreased the activity of luciferase-reporter containing the 3'-untranslated region (UTR) of Chk1 with predicted miR-424-binding site. Moreover, miR-424 expression levels were inversely correlated with Chk1 and p-Chk1 protein levels in both cervical cancer and normal tissues. Furthermore, RNAi-mediated knockdown of Chk1 decreased matrix metalloproteinase 9 expression and phenocopied the tumor suppressive effects of miR-424 in cell models. Taken together, our results identify a crucial tumor suppressive role of miR-424 in the progression of cervical cancer at least partly via upreglating the expression of Chk1 and p-Chk1, and suggest that miR-424 might be a candidate of prognostic predictor or an anticancer therapeutic target for cervical cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Apoptosis / genetics
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Checkpoint Kinase 1
  • Disease Progression
  • Down-Regulation
  • Female
  • G1 Phase / genetics
  • Genes, Tumor Suppressor
  • Humans
  • Matrix Metalloproteinase 9 / metabolism
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Phosphorylation
  • Protein Kinases / biosynthesis*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • S Phase / genetics
  • Transfection
  • Up-Regulation
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*


  • 3' Untranslated Regions
  • MIRN424 microrna, human
  • MicroRNAs
  • Protein Kinases
  • CHEK1 protein, human
  • Checkpoint Kinase 1
  • Matrix Metalloproteinase 9