REST-repressed lncRNA NPPA-AS1 regulates cervical cancer progression by modulating miR-302e/DKK1/Wnt/β-catenin signaling pathway

J Cell Biochem. 2021 Jan;122(1):16-28. doi: 10.1002/jcb.29701. Epub 2020 Sep 23.

Abstract

Long noncoding RNAs (lncRNAs), a group of transcripts, have been revealed to be critical participants in regulating multiple biological processes of malignant tumors. The knowledge of NPPA-AS1 (a new lncRNA) in cancer research is hardly known. Thus, it is of urgent need to study the underlying role of NPPA antisense RNA 1 (NPPA-AS1) in cervical cancer (CC). In this study, NPPA-AS1 was discovered to be lowly expressed and upregulation of it impaired cell proliferation and migration in CC. Besides, downregulation of it led to opposite results. Molecular mechanism assays uncovered that increased expression of NPPA-AS1 could inactivate Wnt/β-catenin signaling pathway in CC. In addition, NPPA-AS1 was found to negatively interact with miR-302e whereas positively correlate with dickkopf-1 (DKK1, an inhibitor of Wnt pathway) in CC. Besides, loss of function assay illuminated that miR-302e inhibition restrained cell proliferation and migration in CC. Subsequent rescue assays confirmed that NPPA-AS1 acted as a competing endogenous RNA in CC by sponging miR-302e to upregulate DKK1 expression. Finally, the RE-1 silencing transcription factor (REST) was testified to function as a transcription suppressor of NPPA-AS1 in CC. In brief, REST-repressed NPPA-AS1 regulates CC progression by modulating miR-302e/DKK1/Wnt/β-catenin signaling pathway.

Keywords: DKK1; NPPA-AS1; REST; cervical cancer; miR-302e.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Atrial Natriuretic Factor / antagonists & inhibitors
  • Atrial Natriuretic Factor / genetics
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • Middle Aged
  • Prognosis
  • RNA, Antisense / genetics
  • RNA, Long Noncoding / genetics*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Survival Rate
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*
  • Wnt1 Protein / genetics
  • Wnt1 Protein / metabolism*
  • Xenograft Model Antitumor Assays
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • Biomarkers, Tumor
  • CTNNB1 protein, human
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • MIRN30e microRNA, human
  • MicroRNAs
  • NPPA protein, human
  • RE1-silencing transcription factor
  • RNA, Antisense
  • RNA, Long Noncoding
  • Repressor Proteins
  • WNT1 protein, human
  • Wnt1 Protein
  • beta Catenin
  • Atrial Natriuretic Factor