A novel long non-coding RNA LINC00524 facilitates invasion and metastasis through interaction with TDP43 in breast cancer

J Cell Mol Med. 2024 Apr;28(8):e18275. doi: 10.1111/jcmm.18275.

Abstract

Breast cancer (BC) remains a significant health concern worldwide, with metastasis being a primary contributor to patient mortality. While advances in understanding the disease's progression continue, the underlying mechanisms, particularly the roles of long non-coding RNAs (lncRNAs), are not fully deciphered. In this study, we examined the influence of the lncRNA LINC00524 on BC invasion and metastasis. Through meticulous analyses of TCGA and GEO data sets, we observed a conspicuous elevation of LINC00524 expression in BC tissues. This increased expression correlated strongly with a poorer prognosis for BC patients. A detailed Gene Ontology analysis suggested that LINC00524 likely exerts its effects through RNA-binding proteins (RBPs) mechanisms. Experimentally, LINC00524 was demonstrated to amplify BC cell migration, invasion and proliferation in vitro. Additionally, in vivo tests showed its potent role in promoting BC cell growth and metastasis. A pivotal discovery was LINC00524's interaction with TDP43, which leads to the stabilization of TDP43 protein expression, an element associated with unfavourable BC outcomes. In essence, our comprehensive study illuminates how LINC00524 accelerates BC invasion and metastasis by binding to TDP43, presenting potential avenues for therapeutic interventions.

Keywords: LINC00524; TDP43; breast cancer; cancer metastasis; protein–RNA interactions.

MeSH terms

  • Biological Assay
  • Breast Neoplasms* / genetics
  • Cell Transformation, Neoplastic
  • Female
  • Gene Ontology
  • Humans
  • RNA, Long Noncoding* / genetics

Substances

  • RNA, Long Noncoding
  • TARDBP protein, human