YY1-inudced activation of lncRNA DUXAP8 promotes proliferation and suppresses apoptosis of triple negative breast cancer cells through upregulating SAPCD2

Cancer Biol Ther. 2021 Mar 4;22(3):216-224. doi: 10.1080/15384047.2021.1881201. Epub 2021 Mar 8.

Abstract

Double homeobox A pseudogene 8 (DUXAP8) belongs to long non-coding RNAs (lncRNAs), which has been proven to promote the biological processes of multiple human cancers. Triple-negative breast cancer (TNBC) is the leading cause of cancer-related death in women worldwide. However, the specific role of lncRNA DUXAP8 and its underlying mechanism in TNBC remains to be unclear. We detected the expression of DUXAP8 in TNBC cells through qRT-PCR analysis. The effects of DUXAP8 silencing on TNBC cell proliferation and apoptosis were identified using CCK-8 assay, EdU assay, flow cytometry analysis and TUNEL assay. The downstream microRNA (miRNA) and messenger RNA (mRNA) of DUXAP8 were searched out through bioinformatics analysis and mechanism experiments. Rescue assays were conducted to verify the involvement of suppressor APC domain containing 2 (SAPCD2) in DUXAP8-mediated TNBC cell proliferation and apoptosis. DUXAP8 was highly expressed in TNBC cells compared to that in normal breast cells. Knockdown of DUXAP8 inhibited TNBC cell proliferation and accelerated cell apoptosis. DUXAP8 interacted with miR-29a-3p and thus enhanced the expression of SAPCD2. Moreover, YY1 transcription factor could bind to DUXAP8 promoter to activate the transcription of DUXAP8. YY1-induced transcriptional activation of DUXAP8 promotes TNBC cell growth through miR-29a-3p/SAPCD2 axis.

Keywords: YY1; competing endogenous RNA (ceRNA); lncRNA DUXAP8; triple-negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Humans
  • Nuclear Proteins / metabolism*
  • RNA, Long Noncoding / genetics*
  • Transfection
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / metabolism*
  • Triple Negative Breast Neoplasms / pathology
  • Up-Regulation
  • YY1 Transcription Factor / metabolism*

Substances

  • Nuclear Proteins
  • RNA, Long Noncoding
  • SAPCD2 protein, human
  • YY1 Transcription Factor
  • YY1 protein, human

Grants and funding

This study was supported by Minhang district science and technology commission fund project [2018MHZ046].