Inhibition of lncRNA PCAT19 promotes breast cancer proliferation

Cancer Med. 2023 May;12(10):11971-11982. doi: 10.1002/cam4.5872. Epub 2023 Mar 29.

Abstract

Background: Breast cancer (BC) is the most common malignancy affecting women. It is vital to explore sensitive biological markers to diagnose and treat BC patients. Recent studies have proved that long noncoding RNAs (lncRNAs) were involved in breast tumor progression. Nonetheless, whether lncRNA prostate cancer-associated transcript 19 (PCAT19) impacts BC development remains unknown.

Methods: We performed various bioinformatic analyses, including machine learning models to identify critical regulatory lncRNAs affecting prognosis in BC. The in situ hybridization (ISH) assay was carried out to confirm the expression levels of lncRNA PCAT19 in tissue specimens. MTT assay, wound healing assay, and transwell assay were performed to investigate PCAT19's impact on proliferation, migration, and invasion of BC cells. Mouse xenografts were used to examine the proliferation-inhibiting function of PCAT19 in vivo.

Results: Among the prognosis-associated lncRNAs, PCAT19 predicted a favorable prognosis in BC. Patients with high expression levels of PCAT19 had a lower clinical stage and less lymph node metastasis. The PCAT19-related genes were enriched in signaling pathways involved in tumor development, indicating PCAT19 was an essential regulator of BC. Using the ISH assay, we confirmed the expression level of lncRNA PCAT19 in human BC tissues was lower than normal breast tissues. Moreover, the knockdown of PCAT19 further confirmed its inhibiting ability in BC cell proliferation. Correspondingly, overexpressing PCAT19 reduced tumor size in mouse xenografts.

Conclusions: Our study demonstrated that lncRNA PCAT19 suppressed the development of BC. PCAT19 might be a promising prognostic biomarker, which provides new insights into risk stratification for BC patients.

Keywords: bioinformatics; breast cancer; long noncoding RNA; tumor biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • MicroRNAs* / genetics
  • Prognosis
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • RNA, Long Noncoding
  • MicroRNAs