Long Non-Coding RNA ARAP1-AS1 Facilitates the Progression of Cervical Cancer by Regulating miR-149-3p and POU2F2

Pathobiology. 2021;88(4):301-312. doi: 10.1159/000507830. Epub 2021 May 7.

Abstract

Background: Emerging research has demonstrated that long non-coding RNAs (lncRNAs) attach great importance to the progression of cervical cancer (CC). LncRNA ARAP1-AS1 was involved in the development of several cancers; however, its role in CC is far from being elucidated.

Methods: Real-time PCR (RT-PCR) was employed to detect ARAP1-AS1 and miR-149-3p expression in CC samples. CC cell lines (HeLa and C33A cells) were regarded as the cell models. The biological effect of ARAP1-AS1 on cancer cells was measured using CCK-8 assay, colony formation assay, flow cytometry, Transwell assay and wound healing assay in vitro, and subcutaneous xenotransplanted tumor model and tail vein injection model in vivo. Furthermore, interactions between ARAP1-AS1 and miR-149-3p, miR-149-3p and POU class 2 homeobox 2 (POU2F2) were determined by bioinformatics analysis, qRT-PCR, Western blot, luciferase reporter and RNA immunoprecipitation assay, respectively.

Results: The expression of ARAP1-AS1 was enhanced in CC samples, while miR-149-3p was markedly suppressed. Additionally, ARAP1-AS1 overexpression enhanced the viability, migration, and invasion of CC cells. ARAP1-AS1 downregulated miR-149-3p via sponging it. ARAP1-AS1 and miR-149-3p exhibited a negative correlation in CC samples. On the other hand, ARAP1-AS1 enhanced the expression of POU2F2, which was validated as a target gene of miR-149-3p.

Conclusion: ARAP1-AS1 was abnormally upregulated in CC tissues and indirectly modulated the POU2F2 expression via reducing miR-149-3p expression. Our study identified a novel axis, ARAP1-AS1/miR-149-3p/POU2F2, in CC tumorigenesis.

Keywords: ARAP1-AS1; Cervical cancer; POU2F2; miR-149-3p.

MeSH terms

  • Animals
  • Carrier Proteins / genetics*
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • GTPase-Activating Proteins / genetics*
  • Gene Expression Regulation, Neoplastic*
  • HeLa Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Octamer Transcription Factor-2 / genetics*
  • Signal Transduction
  • Transplantation, Heterologous
  • Uterine Cervical Neoplasms / genetics*

Substances

  • ARAP1 protein, human
  • Carrier Proteins
  • GTPase-Activating Proteins
  • MIRN149 microRNA, human
  • MicroRNAs
  • Octamer Transcription Factor-2
  • POU2F2 protein, human