Enhanced expression of microtubule-associated protein 7 functioned as a contributor to cervical cancer cell migration and is predictive of adverse prognosis

Abstract

Background: Cervical cancer (CC) is one of the most common female malignancies over the world. Microtubule-associated protein 7 (MAP7) belongs to the family of microtubule-associated proteins (MAPs) which involve in microtubule dynamics and are critical in several important cellular and intracellular activities. This study aimed to investigate the expression and potential role of MAP7 in CC. Methods: The expression level of MAP7 in CC tissues and normal tissues were analyzed using the data obtained from The cancer genomes atlas (TCGA) and genotype-tissue expression (GTEx) databases. The prognostic value of MAP7 in patients with CC was analyzed by Kaplan-Meier analysis, Univariate and Multivariate analyses. Moreover, the influences of MAP7 expression alteration on the viability and motility of Caski, HeLa and C-33A cells was measured by CCK8 assay, colony formation assay, scratch assay, and transwell migration and invasion assays. Flow cytometry was conducted to determine cell apoptosis. Western blot was performed to evaluate the impact of MAP7 on the expression of apoptotic-related proteins as well as mitogen-activated protein kinase (MAPK) signaling pathway-related proteins. In vivo tumorigenicity assay was performed to explore the influence of MAP7 on tumor growth. Results: Up-regulation of MAP7 was observed in CC tissues and high MAP7 expression was positively correlated with worse prognosis. Multivariate analyses suggested that MAP7 expression can be served as an independent predictor for overall survival of patients with CC. Knockdown of MAP7 markedly suppressed Caski and HeLa cell viability, migration and invasion while notably induced cell apoptosis. Furthermore, depletion of MAP7 in Caski and HeLa cells elevated the expression levels of Active-caspase 3 and Bax, but declined the level of Bcl-2. Whilst, overexpression of MAP7 in C-33A cells presented the opposite outcomes. Additionally, knockdown of MAP7 significantly decreased the phosphorylation of mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK) in Caski and HeLa cells, and overexpression of MAP7 increased their phosphorylation in C-33A cells, indicating that MAP7 may regulate the MAPK signaling pathway in CC cells. In vivo assays revealed that knockdown of MAP7 remarkably repressed the growth of CC tumors. Conclusion: The results of the present study suggest that MAP7 functions as a promoter during the occurrence and progression of CC, and that MAP7 may serve as a promising therapeutic target in CC.