LncRNA WEE2-AS1 promotes proliferation and inhibits apoptosis in triple negative breast cancer cells via regulating miR-32-5p/TOB1 axis

Biochem Biophys Res Commun. 2020 Jun 11;526(4):1005-1012. doi: 10.1016/j.bbrc.2020.01.170. Epub 2020 Apr 16.

Abstract

Triple negative breast cancer (TNBC) is a malignant breast cancer subtype with poor prognosis. Recent studies have revealed the critical roles of dysregulated long non-coding RNAs (lncRNAs) in many cancer types, including TNBC. LncRNA WEE2 antisense RNA 1 (WEE2-AS1) has been reported to be able to promote the progression of hepatocellular carcinoma, but the function of WEE2-AS1 in TNBC is still unknown. Therefore, in this study, we specifically researched the role of WEE2-AS1 and probed its molecular mechanism in TNBC cells. Our results showed that WEE2-AS1 was up-regulated in TNBC cell lines, and WEE2-AS1 knockdown could inhibit TNBC cell proliferation, promote apoptosis, and suppress migration and invasion. Further, we found that miR-32-5p was down-regulated in TNBC cells and could be sponged by WEE2-AS1. Moreover, miR-32-5p could target its downstream gene transducer of ERBB2, 1 (TOB1), which was highly expressed and could play the oncogenic role in TNBC cells. Through rescue assays, we proved that WEE2-AS1/miR-32-5p/TOB1 axis could modulate cancer progression in TNBC cells. In conclusion, our results demonstrated the oncogenic function of lncRNA WEE2-AS1 in TNBC cells, providing a novel insight into TNBC therapy.

Keywords: TOB1; Triple negative breast cancer; WEE2-AS1; miR-32-5p.

MeSH terms

  • Apoptosis / genetics*
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction / genetics
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology*
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • MIRN32 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • TOB1 protein, human
  • Tumor Suppressor Proteins