Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1/microRNA-202-3p/periostin axis modulates invasion and epithelial-mesenchymal transition in human cervical cancer

J Cell Physiol. 2019 Aug;234(8):14170-14180. doi: 10.1002/jcp.28113. Epub 2019 Jan 11.

Abstract

The human cervical cancer (CC) has been identified as one of the most common tumors in women, and the molecular regulation in CC still remains unclear. The dysregulation of periostin has been found in a variety of cancers, but whether it is involved in the regulation of CC is unknown. The present study aimed to investigate the biological roles of periostin in CC and to explore the potential molecular regulation mechanisms. Here we found that the expression of periostin was overexpressed in CC tissues and CC cell lines (HeLa and SiHa). Knockdown of periostin in HeLa or SiHa cells significantly decreased cell viability, cell migration and invasion, and reduced epithelial-mesenchymal transition (EMT). Moreover, periostin knockdown suppressed the activation of Akt/the mammalian target of rapamycin (mTOR) signaling pathway, which is crucial for periostin to regulate the above biological activities in CC cells. Furthermore, we found that the periostin expression was positively correlated with the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and negatively correlated with the expression of microRNA (miR)-202-3p in CC tissues. We confirmed that MALAT1 positively regulated the expression of periostin by negatively modulating miR-202-3p. In addition, the MALAT1/miR-202-3p/periostin axis was deeply associated with the regulation of the cell viability, cell migration and invasion, and EMT in CC cells. Taken together, these findings suggest that periostin, which can be regulated by the MALAT1-miR-202-3p axis, plays an important role in regulating cell viability, cell migration and invasion, and EMT of CC cells via activating Akt/mTOR signaling.

Keywords: cell invasion; cervical cancer (CC); epithelial-mesenchymal transition (EMT); metastasis-associated lung adenocarcinoma transcript 1 (MALAT1); microRNA-202-3p; periostin.

MeSH terms

  • Cell Adhesion Molecules / genetics*
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • RNA, Long Noncoding / genetics*
  • Signal Transduction / genetics
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Cell Adhesion Molecules
  • MALAT1 long non-coding RNA, human
  • MIRN202 microRNA, human
  • MicroRNAs
  • POSTN protein, human
  • RNA, Long Noncoding