An overview of lncRNA NEAT1 contribution in the pathogenesis of female cancers; from diagnosis to therapy resistance

Gene. 2025 Jan 15:933:148975. doi: 10.1016/j.gene.2024.148975. Epub 2024 Sep 29.

Abstract

Despite the ongoing progress in detecting and treating cancer, there is still a need for extensive research into the molecular mechanisms involved in the emergence, progression, and resistance to recurrence of female reproductive tissue-specific cancers such as ovarian, breast, cervical, and endometrial cancers. The nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA (lncRNA) that exhibits increased expression in female tumors. Moreover, elevated levels of NEAT1 have been associated with poorer survival outcomes in cancer patients. NEAT1 plays a pivotal role in driving tumor initiation through modulating the expression of genes involved in various aspects of tumor cell proliferation, epithelial-to-mesenchymal transition (EMT), metastasis, chemoresistance, and radio-resistance. Mechanistically, NEAT1 acts as a scaffold RNA molecule via interacting with EZH2 (Enhancer of Zeste 2 Polycomb Repressive Complex 2 Subunit), thereby influencing the expression of downstream effectors of EZH2. Additionally, NEAT1 functions as a competing endogenous RNA (ceRNA) by microRNAs (miRNAs) sponging, consequently altering the expression levels of their target genes during the development of female cancers. This comprehensive review aims to shed light on the latest insights regarding the expression pattern, biological functions, and underlying mechanisms governing the function and regulation of NEAT1 in tumors. Furthermore, particular emphasis is placed on its clinical significance as a novel diagnostic biomarker and a promising therapeutic target for female cancers.

Keywords: Chemoresistance; Female cancer; Metastasis; lncRNA NEAT1; miRNA.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / genetics
  • Cell Proliferation / genetics
  • Drug Resistance, Neoplasm* / genetics
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism
  • Epithelial-Mesenchymal Transition* / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics
  • RNA, Long Noncoding* / genetics

Substances

  • RNA, Long Noncoding
  • NEAT1 long non-coding RNA, human
  • MicroRNAs
  • Biomarkers, Tumor
  • Enhancer of Zeste Homolog 2 Protein