DANCR-mediated microRNA-665 regulates proliferation and metastasis of cervical cancer through the ERK/SMAD pathway

Cancer Sci. 2019 Mar;110(3):913-925. doi: 10.1111/cas.13921. Epub 2019 Jan 19.


Emerging evidence has indicated that microRNAs (miRNAs) play an important role in cervical cancer (CC). However, the role of miRNA (miR)-665 in cervical cancer remains unclear. The aim of the present study was to investigate the potential functions of miR-665 in CC and to identify the underlying mechanisms of action. Herein, we show that miR-665 was downregulated in CC tissues and cell lines, which is negatively correlated with tumor size, distant metastasis, advanced TNM stage and poor prognosis. Functionally, miR-665 inhibited cell proliferation, migration and invasion and resistance of cisplatin for CC cells, as well as tumor growth. We validated that transforming growth factor beta receptor 1 (TGFBR1) was a direct target of miR-665 and mediated the ERK/SMAD pathway. In addition, we identified miR-665 as the competing endogenous RNA for long noncoding (lnc)-DANCR. These observations suggested that lnc-DANCR-mediated miR-665 downregulation regulates the malignant phenotype of CC cells by targeting TGFBR1 through the ERK/SMAD pathway, which may present a pathway for novel therapeutic stratagems for CC therapy.

Keywords: DANCR; ERK/SMAD; TGFBR1; cervical cancer; miR-665.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • HeLa Cells
  • Humans
  • MAP Kinase Signaling System / genetics*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Metastasis / genetics*
  • Neoplasm Metastasis / pathology
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Receptor, Transforming Growth Factor-beta Type I / genetics
  • Smad Proteins / genetics*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology


  • DANCR long noncoding RNA, human
  • MIRN665 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Smad Proteins
  • Receptor, Transforming Growth Factor-beta Type I