lncRNA MCM3AP-AS1 inhibits the progression of colorectal cancer via the miR-19a-3p/FOXF2 axis

J Gene Med. 2021 Mar;23(3):e3306. doi: 10.1002/jgm.3306. Epub 2021 Jan 19.

Abstract

Background: Long non-coding RNA MCM3AP antisense RNA 1 (lncRNA MCM3AP-AS1) has a regulatory role in the development of diverse malignancies, whereas its role and mechanism in colorectal cancer (CRC) is not yet clear.

Methods: The relative expression of MCM3AP-AS1, miR-19a-3p and forkhead box F2 (FOXF2) mRNA in 53 cases of CRC and its adjacent normal tissues, human normal colonic mucosal cells (FHC cells) and CRC cell lines was examined by a quantitative real-time polymerase chain reaction, and the changes of cell multiplication and migration were examined by the cell counting kit-8 method, EdU test, and scratch-healing test, respectively. Bioinformatics, dual-luciferase reporter gene assay and a RNA immunoprecipitation experiment were adopted to predict and verify the relationship between MCM3AP-AS1 and miR-19a-3p; bioinformatics and dual-luciferase reporter gene assay were adopted to predict and verify the relationship between miR-19a-3p and FOXF2. Western blotting was executed to examine the effects of MCM3AP-AS1 overexpression or knockdown on FOXF2 protein expression.

Results: MCM3AP-AS1 expression was down-modulated in CRC, and its dysregulation was linked to unfavorable pathological characteristics. MCM3AP-AS1 significantly impeded the multiplication and migration of CRC cells. MCM3AP-AS1 was recognized as a molecular sponge to suppress miR-19a-3p expression, and FOXF2 was a target gene of miR-19a-3p. MCM3AP-AS1 positively modulated FOXF2 expression, and its biological effect was dependent the on miR-19a-3p/FOXF2 axis.

Conclusions: MCM3AP-AS1 can inhibit CRC promoting by modulating the miR-19a-3p/FOXF2 axis.

Keywords: colorectal cancer; lncRNA MCM3AP antisense RNA 1; migration; multiplication.

MeSH terms

  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism*
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Disease Progression
  • Female
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Neoplasm Metastasis
  • RNA, Antisense / genetics
  • RNA, Antisense / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction

Substances

  • FOXF2 protein, human
  • Forkhead Transcription Factors
  • Intracellular Signaling Peptides and Proteins
  • MIRN19 microRNA, human
  • MicroRNAs
  • RNA, Antisense
  • RNA, Long Noncoding
  • Acetyltransferases
  • MCM3AP protein, human