lncRNA prostate cancer-associated transcript 18 upregulates activating transcription factor 7 to prevent metastasis of triple-negative breast cancer via sponging miR-103a-3p

Bioengineered. 2021 Dec;12(2):12070-12086. doi: 10.1080/21655979.2021.2003928.

Abstract

Long non-coding RNA (lncRNA) prostate cancer-associated transcript 18 (PCAT18) is a potential diagnostic target for adenocarcinoma. However, its role in triple-negative breast cancer (TNBC) remains largely unknown. Based on data from an online database, a significant decline in lncRNA PCAT18 was observed in patients with TNBC subtype compared to a population with normal breast tissue. Patients with TNBC with high PCAT18 levels presented good outcomes. Patients with TNBC with high PCAT18 had a lower rate of lymph node-positive metastasis than those with low PCAT18. PCAT18-upregulation inhibited, while PCAT18-downregulation promoted, migration and expression of matrix metalloproteinases 9/2 (MMP9/MMP2) and uridylyl phosphate adenosine (uPA) in TNBC cells. Activating transcription factor 7 (ATF7) was positively associated with PCAT18, and ATF7-inhibition abrogated the anti-migration effects of PCAT18 on TNBC cells. Mechanistically, miR-103a-3p directly targeted and inhibited ATF7 expression. PCAT18 competitively sponges miR-103a-3p, promoting the expression of ATF7. Exogenous PCAT18 was associated with lower incidence of lung metastasis followed by the upregulation of ATF7, which was prevented by the treatment of miR-103a-3p mimics. Collectively, PCAT18 was expressed at low levels in TNBC, and PCAT18 could sponge miR-103a-3p and promote ATF7 expression, resulting in prevention of TNBC metastasis. Thus, PCAT18 can serve as a predictive factor for patients with metastatic TNBC.

Keywords: LncRNA PCAT18; MiR-103a-3p; Triple-negative breast cancer; activating transcription factor 7; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factors / genetics*
  • Activating Transcription Factors / metabolism
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / secondary*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology*
  • Up-Regulation / genetics*

Substances

  • ATF7 protein, human
  • Activating Transcription Factors
  • Extracellular Matrix Proteins
  • MIRN103 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding

Grants and funding

This study was supported by the Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translation Research of Hakka Population (Grant No.: 2018B030322003), the Science and Technology Program of Meizhou (Grant No.: 2019B0202001), and the Scientific Research Cultivation Project of Meizhou People's Hospital (Grant No.: PY-C2020020 and PY-C2020031).