Long non-coding RNA CASC9 enhances breast cancer progression by promoting metastasis through the meditation of miR-215/TWIST2 signaling associated with TGF-β expression

Biochem Biophys Res Commun. 2019 Aug 6;515(4):644-650. doi: 10.1016/j.bbrc.2019.05.080. Epub 2019 Jun 6.

Abstract

Accumulating study has indicated that long non-coding RNAs (lncRNAs) could serve as critical modulators to meditate tumor metastasis. In the study, the crucial role of lncRNA cancer susceptibility candidate 9 (CASC9) in regulating cervical cancer metastasis and progression was investigated. CASC9 expression was markedly increased in cervical cancer tissues and cell lines. Cervical cancer patients with low CASC9 expression showed better overall survival rate. Moreover, cancer-associated fibroblasts (CAFs)-derived transforming growth factor β (TGF-β) could increase CASC9 expression. The crosslink between CAFs and cervical cancer cells led to CASC9 to elevate the metastasis of cervical cancer cells. CASC9 dysregulation could function as a miRNA sponge to competitively protect twist homolog 2 (TWIST2) mRNA 3'UTR from miR-215. Results in this study indicated the effects of CASC9 on cervical cancer and suggested a novel axis by which CASC9 meditated cervical cancer cell metastasis and proliferation both in vivo and in vitro. Together, CASC9 could be a prognostic marker for cervical cancer to develop effective therapeutic treatment against cervical cancer growth.

Keywords: CASC9; Cervical cancer; Metastasis; MiR-215; TWIST2.

MeSH terms

  • Animals
  • Cervix Uteri / metabolism
  • Cervix Uteri / pathology
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • Neoplasm Metastasis*
  • Neoplasm Transplantation
  • RNA, Long Noncoding / genetics*
  • Repressor Proteins / metabolism*
  • Transforming Growth Factor beta1 / metabolism*
  • Twist-Related Protein 1 / metabolism*
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • MIRN215 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Repressor Proteins
  • TGFB1 protein, human
  • TWIST2 protein, human
  • Transforming Growth Factor beta1
  • Twist-Related Protein 1
  • long noncoding RNA CASC9, human