circ_0038718 promotes colon cancer cell malignant progression via the miR-195-5p/Axin2 signaling axis and also effect Wnt/β-catenin signal pathway

BMC Genomics. 2021 Oct 27;22(1):768. doi: 10.1186/s12864-021-07880-z.

Abstract

Objective: Colon cancer (CC) is one of the most common cancers whose progression is regulated by a number of factors, including circular RNAs (circRNAs). Nonetheless, circ_0038718 is a novel circRNA, and its regulatory mechanism in CC remains unclear.

Methods: Real-time quantitative PCR (qRT-PCR) was performed to detect the expression of circ_0038718, miR-195-5p and Axin2. Western blot was conducted to determine the protein expression of Axin2 and the key proteins on Wnt/β-catenin signaling pathway. Oligo (dT) 18 primers and RNase R were employed to identify the circular features of circ_0038718, and the location of circ_0038718 in cells was detected via nucleocytoplasmic separation. Dual-luciferase reporter assay and RNA binding protein immunoprecipitation experiment were carried out to investigate the molecular mechanism of circ_0038718/miR-195-5p/Axin2. Additionally, MTT assay was conducted to assess cell proliferation; Transwell assay was performed to evaluate cell migration and invasion, respectively. The effect of circ_0038718 on CC tumor growth was tested through tumor formation in nude mice.

Results: circ_0038718 was highly expressed in CC and could sponge miR-195-5p in cytoplasm. Silencing circ_0038718 suppressed the proliferative, migratory and invasive abilities of CC cells, while the promoting effect of high circ_0038718 expression on CC cells was reversed upon miR-195-5p over-expression. Axin2 was a downstream target of miR-195-5p and could regulate the Wnt/β-catenin signaling pathway. Axin2 expression was modulated by circ_0038718/miR-195-5p. Knockdown of Axin2 could also attenuate the promoting effect of high circ_0038718 expression on CC cell malignant progression, thus inhibiting tumor growth.

Conclusion: circ_0038718 is able to facilitate CC cell malignant progression via the miR-195-5p/Axin2 axis, which will provide a new idea for finding a novel targeted treatment of CC.

Keywords: Invasion; Migration; Proliferation; Wnt/β-catenin signaling pathway; circ_0038718; colon cancer.

MeSH terms

  • Animals
  • Axin Protein / genetics
  • Cell Line, Tumor
  • Colonic Neoplasms* / genetics
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • RNA, Circular / genetics*
  • Wnt Signaling Pathway* / genetics
  • beta Catenin

Substances

  • Axin Protein
  • Axin2 protein, mouse
  • MIRN195a microRNA, mouse
  • MicroRNAs
  • RNA, Circular
  • beta Catenin