Circ-TFCP2L1 Promotes the Proliferation and Migration of Triple Negative Breast Cancer through Sponging miR-7 by Inhibiting PAK1

J Mammary Gland Biol Neoplasia. 2019 Dec;24(4):323-331. doi: 10.1007/s10911-019-09440-4. Epub 2019 Nov 27.

Abstract

CircRNAs are essential factors that have been verified to regulate various forms of carcinogenesis. However, the role of circRNAs in triple negative breast cancer (TNBC) tumourigenesis is not well clarified. In this study, we explored the circRNA expression profiles and possible modulation mechanism of circRNAs on triple negative breast cancer tumourigenesis. We used three pairs of triple negative breast cancer tissues and adjacent noncancerous tissues to perform a human circRNA microarray for screening of circRNA expression patterns in TNBC. The results showed that circ-TFCP2L1 was significantly up-regulated in TNBC tissues and cells, tending to have a shorter disease-free survival of TNBC patients. In vitro loss-of-function experiments showed that knockdown of circ-TFCP2L1 significantly suppressed the proliferation and migration of TNBC cells. Moreover, the results showed that the proliferation and migration capabilities and PAK1 expression in TNBC cells treated with si-circ-TFCP2L1 + miR-7 mimics were significantly suppressed compared with the normal group. Therefore, circ-TFCP2L1 was identified as a sponge of miR-7 functionally targeting PAK1 and further promoting the proliferation and migration of TNBC cells. Taken together, the results from our study reveal a novel regulatory mechanism and offer novel insight into the role of circ-TFCP2L1 in progression of triple negative breast cancer.

Keywords: Microarray; Migration; Proliferation; Sponge; circRNAs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Movement*
  • Cell Proliferation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics*
  • RNA, Circular / genetics*
  • Repressor Proteins / genetics*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology*
  • Tumor Cells, Cultured
  • p21-Activated Kinases / genetics
  • p21-Activated Kinases / metabolism*

Substances

  • Biomarkers, Tumor
  • MIRN7 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Repressor Proteins
  • TFCP2L1 protein, human
  • PAK1 protein, human
  • p21-Activated Kinases