miR-195-5p Inhibits Colon Cancer Progression via KRT23 Regulation.

BACKGROUND/OBJECTIVES: KRT23 was recently discovered as an epithelial-specific intermediate filament protein in the type I keratin family. Many studies have underlined keratin's involvement in several biological processes as well as in the pathogenesis of different diseases. Specifically, KRT23 was reported to affect the structural integrity of epithelial cells and to trigger cellular signaling leading to the onset of cancer. The aim of this study is to characterize a novel mechanism based on miR-195-5p/KRT23 in colorectal cancer.

METHODS

KRT23 mRNA and protein expression were characterized in FFPE sections from patients with CRC. The effects of miR-195-5p on KRT23 expression at the mRNA and protein levels were assessed by transient transfection experiments with mimic and inhibitor molecules. Cell attachment/detachment, migration, invasion, clone formation, and apoptosis were evaluated in human CRC cell lines after miR-195-5p mimic transfection.

RESULTS

We identified KRT23 as a putative target of miR-195-5p, a microRNA that we previously demonstrated to be reduced in CRC. We have proved the KRT23 expression deregulation in the tumoral section compared to adjacent normal mucosa in patients with CRC, according to the data derived from the public repository. We proved that the gain of miR-195-5p decreased the KRT23 expression. Conversely, we demonstrated that the inhibition of miR-195-5p led to an increase in KRT23 expression levels. We have demonstrated the in vitro effectiveness of miR-195-5p on CRC progression and that the in vivo intraperitoneal delivery of miR-195-5p mimic lowered colonic KRT23 mRNA and protein expression.

CONCLUSIONS

These findings highlight a new regulatory mechanism by miR-195-5p in CRC affecting the keratin intermediate filaments and underline the miR-195-5p potential clinical properties.