NR2F2-AS1 accelerates cell proliferation through regulating miR-4429/MBD1 axis in cervical cancer

Biosci Rep. 2020 Jun 26;40(6):BSR20194282. doi: 10.1042/BSR20194282.

Abstract

Cervical cancer is one of the most frequent malignant tumors in female. Increasing studies have demonstrated that long noncoding RNAs (lncRNAs) play a key role in the development of multiple cancers. Although some studies have confirmed that lncRNA NR2F2 antisense RNA 1 (NR2F2-AS1) is a pro-cancer gene in many cancers, the molecular mechanism of NR2F2-AS1 in cervical cancer has not been completely elucidated. In the present study, our results revealed that NR2F2-AS1 expression was up-regulated in cervical cancer tissues and cells, notably in patients with advanced cervical cancer. NR2F2-AS1 accelerated progression of cervical cancer by facilitating cell proliferation, migration, invasion, and EMT process, but inhibiting cell apoptosis. Moreover, NR2F2-AS1 acted as a molecular sponge of miR-4429 and methyl-CpG-binding domain protein 1 (MBD1) was a downstream target of miR-4429 in cervical cancer. Furthermore, there was a negative correlation between miR-4429 expression and NR2F2-AS1 or MBD1 expression in tumor tissues. Rescue experiments confirmed that MBD1 overexpression partly rescued NR2F2-AS1 knockdown-mediated inhibition of progression in cervical cancer. To sum up, these results suggested the potential mechanism of NR2F2-AS1 in cervical cancer and revealed that NR2F2-AS1 exerted its carcinogenic effect via regulating miR-4429/MBD1 axis, indicating a promising insight into the therapeutic target of cervical cancer.

Keywords: MBD1; NR2F2-AS1; cervical cancer; miR-4429.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Movement
  • Cell Proliferation*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Disease Progression
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • DNA-Binding Proteins
  • MBD1 protein, human
  • MIRN4429 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Transcription Factors