CKAP2L Plays a Pivotal Role in Colorectal Cancer Progression via the Dual Regulation of Cell Cycle and Epithelial-Mesenchymal Transition.

Abstract

Background: Cytoskeleton-associated protein 2 like (CKAP2L) has been demonstrated to mediate the cell cycle in cancer cells. However, it is unknown whether CKAP2L impacts colorectal cancer (CRC). The purpose of this study was to investigate the role of CKAP2L in CRC.

Methods: CKAP2L and regulatory factor X 5 (RFX5) expression profiles in colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ) were analyzed in UALCAN. Human colorectal adenocarcinoma epithelial cells, DLD1, were transfected with small interfering RNA targeting RFX5 and CKAP2L-overexpressing vectors (OE-CKAP2L). The interaction between CKAP2L and RFX5 was identified by dual-luciferase assay and chromatin immunoprecipitation. Epithelial-mesenchymal transition (EMT)- and protein kinase B/mammalian target of the rapamycin (AKT/mTOR) pathway-associated proteins were evaluated by western blotting.

Results: RFX5 and CKAP2L expression was increased in CRC based on the UALCAN database. RFX5 downregulation inhibited proliferation, migration, invasion, and EMT while promoting G1/S phase arrest (p < 0.01). RFX5 knockdown downregulated CKAP2L expression and mediated the inactivation of the AKT/mTOR pathway (p < 0.001). RFX5 acted as an upstream transcription factor of CKAP2L. CKAP2L overexpression attenuated the restriction of RFX5 downregulation on CRC cell malignant phenotypes (p < 0.01).

Conclusion: CKAP2L transcriptionally activated by RFX5 accelerates CRC proliferation and metastasis by promoting the cell cycle and EMT. This study provides potential molecular targets for treating CRC.