Abstract
Ensconsin is encoded by the MAP7 gene and belongs to the microtubule-associated proteins. This study aimed to explore its functional roles and partners in cell-cycle progression in cervical cancer. Data from the Cancer Genome Atlas-Cervical & Endocervical Cancer (TCGA-CESC) and the Genotype-Tissue Expression project were used for bioinformatic analysis. SiHa cells were used for in-vitro and in-vivo analysis. Co-immunoprecipitation (Co-IP) assay was conducted to explore the proteins interacted with MAP7. Results showed that MAP7 mRNA expression might serve as an independent biomarker of shorter survival. MAP7 overexpression elevated cyclin D1/cyclin B1 expression, facilitated cell-cycle progression and promoted SiHa cell growth in a xenograft tumor model. Co-IP experiments confirmed a novel interaction between MAP7 and RC3H1. Knockdown of either RC3H1 or MAP7 significantly attenuated cyclin D1/cyclin B1 upregulation, and cell-cycle progression induced by the other partner. MAP7 overexpression led to increased expression of P-IKK (Ser176/177) and P-p65 (Ser536). RC3H1 inhibition abrogated MAP7 induced upregulation of P-IKK and P-p65. Data in TCGA-CESC showed that MAP7 expression was positively correlated with its copy number segments, but was negatively correlated with the methylation level of three CpG sites within the gene locus. Demethylation treatment by 5-Aza-dC elevated both MAP7 mRNA and protein expression in a dose-dependent manner. In conclusion, this study revealed a novel interaction between MAP7 and RC3H1 in cervical cancer cells, which cooperatively enhanced cyclin D1/cyclin B1 expression and facilitated cell-cycle progression. These effects were at least partly mediated by activated canonical IKK/NF-kB signaling.