The anti-tumor effect of miR-539-3p on colon cancer via regulating cell viability, motility, and nude mouse tumorigenicity with CDK14 inhibition

J Gastrointest Oncol. 2020 Oct;11(5):899-910. doi: 10.21037/jgo-20-387.

Abstract

Background: Colon cancer is one of the major causes of morbidity and mortality worldwide. MicroRNAs (miRNAs) play important functions in the growth and metastasis of colon cancer. This study aimed to investigate the anti-tumor effect of micro ribonucleic acid 539-3p (miR-539-3p) on colon cancer via regulation of cell viability, motility, and nude mouse tumorigenicity with cyclin-dependent kinase 14 (CDK14) inhibition.

Methods: The target relationship between miR-539-3p and CDK14 was predicted using TargetScan software, and were detected by luciferase reporter assay. Cell counting kit-8 (CCK-8) assay and flow cytometry were employed to examine cell proliferation and apoptosis. Western blotting was employed to measure the protein expression levels of p27, cleaved caspase-3, and epithelial (E)- and neural (N)-cadherin. The effect of miR-539-3p on tumor growth was evaluated by establishing a xenograft tumor model in nude mice.

Results: The target relationship of CDK14 and miR-539-3p was identified as a negative regulator. Overexpression of miR-539-3p significantly inhibited SW620 and SW480 cell proliferation, promoted cell apoptosis, and suppressed cell invasion by targeting CDK14. The xenograft tumor model showed that the overexpression of miR-539-3p reduced tumor weight and volume. Immunohistochemical staining revealed that the overexpression of miR-539-3p inhibited the expression of Ki67 and E-cadherin. Additionally, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining showed that overexpression of miR-539-3p induced apoptosis.

Conclusions: Overexpression of miR-539-3p inhibited SW620 and SW480 cell proliferation, promoted cell apoptosis, and suppressed cell invasion by targeting CDK14. Therefore, miR-539-3p may be a useful diagnostic and therapeutic biomarker for colon cancer.

Keywords: CDK14; Colon cancer; apoptosis; invasion; miR-539-3p; proliferation.