MicroRNA-362 is downregulated in cervical cancer and inhibits cell proliferation, migration and invasion by directly targeting SIX1

Oncol Rep. 2017 Jan;37(1):501-509. doi: 10.3892/or.2016.5242. Epub 2016 Nov 15.


Cervical cancer is the second most common type of cancer in women accounting for 12% of all human cancers in the world. Mounting evidence demonstrates that microRNAs play important roles in the carcinogenesis and progression of cervical cancer. The aim of this study was to investigate the expression, roles and molecular mechanism of microRNA-362 (miR-362) in cervical cancer. According to the results, we found that expression level of miR-362 was significantly reduced in cervical cancer tissues and cell lines. Low miR-362 expression was correlated with FIGO stage, lymph node metastasis and vascular invasion in cervical cancer. Functional assays showed that restoration of miR-362 repressed cell proliferation, migration and invasion in cervical cancer. We also provided direct evidence that sineoculis homeobox homolog 1 (SIX1) was a direct target of miR-362 in cervical cancer, which was confirmed by bioinformatics analysis, luciferase reporter assay, qRT-PCR and western blot analysis. SIX1 was upregulated in cervical cancer and inversely correlated with miR‑362 expression in cervical cancer. In addition, SIX1 knockdown could simulate the roles of miR-362 overexpression on cell proliferation, migration and invasion of cervical cancer. Moreover, rescue experiments indicated that restoration of SIX1 was sufficient to abolish proliferation, migration and invasion induced by miR-362 overexpression in cervical cancer cells. The newly identified miR-362/SIX1 pathway provides insight into cervical cancer progression, and may represent a novel therapeutic target.

Publication types

  • Retracted Publication

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Cells, Cultured
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • HeLa Cells
  • Homeodomain Proteins / genetics*
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / physiology
  • Middle Aged
  • Neoplasm Invasiveness
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology


  • Homeodomain Proteins
  • MIRN362 microRNA, human
  • MicroRNAs
  • SIX1 protein, human