miR-144-3p inhibits cell proliferation of colorectal cancer cells by targeting BCL6 via inhibition of Wnt/β-catenin signaling

Cell Mol Biol Lett. 2020 Mar 17:25:19. doi: 10.1186/s11658-020-00210-3. eCollection 2020.

Abstract

Background: It has been shown that miR-144-3p regulates cell proliferation, apoptosis, migration and invasion in various cancers. However, the function and expression of miR-144-3p in colorectal cancer (CRC) remained obscure.

Methods: Immunohistochemical (IHC) staining was performed to investigate the protein expression of BCL6 in CRC tissues. The effect of BCL6 and miR-144-3p on CRC cells was explored through methylthiazolyl tetrazolium (MTT) assay, colony formation and cell cycle assays. Luciferase reporter assays, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were carried out to determine that BCL6 is directly regulated by miR-144-3p.

Results: Our results showed that miR-144-3p is down-regulated in CRC and correlates with the tumor progression of CRC patients. miR-144-3p inhibits cell proliferation and delays G1/S phase transition of CRC cells. Moreover, we found that BCL6 is a new target of miR-144-3p. Furthermore, BCL6 is a mediator of miR-144-3p repression of cell proliferation and cell cycle arrest in CRC cells. miR-144-3p repression of Wnt/β-catenin signaling is mediated by BCL6 in CRC cells.

Conclusions: Overall, the effect of the miR-144-3p/BCL6 axis on regulating CRC carcinogenesis was demonstrated, and miR-144-3p was identified as a potential prognostic and therapeutic target in colorectal cancer.

Keywords: BCL6; CRC; Wnt/β-catenin; miR-144-3p; miRNA.

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Cell Survival / genetics
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-6 / genetics
  • Proto-Oncogene Proteins c-bcl-6 / metabolism*
  • S Phase Cell Cycle Checkpoints / genetics
  • Wnt Signaling Pathway / genetics*
  • beta Catenin / metabolism

Substances

  • BCL6 protein, human
  • MIRN144 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-6
  • beta Catenin