DDN-AS1-miR-15a/16-TCF3 feedback loop regulates tumor progression in cervical cancer

J Cell Biochem. 2019 Jun;120(6):10228-10238. doi: 10.1002/jcb.28307. Epub 2018 Dec 23.

Abstract

Cervical cancer (CC) is known as one of the most common gynecological tumors. Long noncoding RNAs (lncRNAs) are a group of regulators that have been widely reported in human malignant tumors including CC. On the basis of the data of The Cancer Genome Atlas, lncRNA DDN and PRKAG1 antisense RNA 1 ( DDN-AS1) that is overexpressed in CC tissues predicted poor prognosis for patients with CC. Moreover, quantitative reverse transcription PCR analysis further identified the upregulation of DDN-AS1 in CC tissues and cell lines. Loss-of-function assays revealed that knockdown of DDN-AS1 suppressed CC progression by efficiently inhibiting cell proliferation, migration, and invasion. Mechanism investigations revealed that DDN-AS1 was upregulated by its upstream transcription activator transcription factor 3 ( TCF3). Moreover, DDN-AS1 increased the expression of TCF3 by competitively binding miR-15a and miR-16. In conclusion, DDN-AS1-miR-15a/16-TCF3 feedback loop contributes to cell proliferation, migration, and invasion in CC.

Keywords: cervical cancer; lncRNA DDN and PRKAG1 antisense RNA 1; miR-15a/16; migration; transcription factor 3.

MeSH terms

  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Feedback, Physiological
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HeLa Cells
  • Humans
  • Kaplan-Meier Estimate
  • MicroRNAs / genetics*
  • RNA, Long Noncoding / genetics*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • MIRN15 microRNA, human
  • MIRN16 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • TCF3 protein, human