MicroRNA-188-5p targeting Forkhead Box L1 promotes colorectal cancer progression via activating Wnt/β-catenin signaling

Oncol Res. 2022 Jul 13;29(2):119-128. doi: 10.32604/or.2022.03178. eCollection 2021.

Abstract

Objective: MicroRNA-188-5p (miR-188) enhances oncologic progression in various human malignancies. This study aimed to explore its role in colorectal cancer (CRC).

Materials and methods: Human CRC tissues paired with normal tissues, and several CRC cell lines were utilized. Real-time quantitative PCR was applied to measure the expression of miR-188. Overexpression and knockdown were used to access the function of miR-188 and to investigate whether FOXL1/Wnt signaling mediates such function. The proliferation, migration and invasion of cancer cells were evaluated by CCK8, wound-healing and transwell assays, respectively. Whether FOXL1 acted as a direct target of miR-188 was verified by dual-luciferase reporter assays.

Results: Levels of miR-188 were upregulated in CRC tissues than in paired-normal tissues, as well as in various CRC cell lines. High expression of miR-188 was strongly associated with advanced tumor stage, accompanied with significant tumor cell proliferation, invasion and migration. It was confirmed that FOXL1 played positive crosstalk between miR-188 regulation and downstream Wnt/β-catenin signaling activation.

Conclusions: All findings indicate that miR-188 promotes CRC cell proliferation and invasion through targeting FOXL1/Wnt signaling and could be served as a potential therapeutic target for human CRC in the future.

Keywords: Colorectal adenocarcinoma; Oncogenesis; Oncologic progression; Wnt signaling; miR-188.

MeSH terms

  • Cell Line
  • Colorectal Neoplasms* / genetics
  • Humans
  • MicroRNAs* / genetics
  • Wnt Signaling Pathway / genetics
  • beta Catenin

Substances

  • beta Catenin
  • MicroRNAs
  • MIRN188 microRNA, human