MAP kinase-interacting kinase 1 (MNK1) plays as a tumor suppressor in bladder cancer

Transl Cancer Res. 2020 Apr;9(4):2588-2598. doi: 10.21037/tcr.2020.02.67.

Abstract

Background: MAP kinase-interacting kinase 1 (MNK1) has been reported to be over-expressed in several cancers, however, its expression level and biological function in bladder cancer (BCa) remains unclear.

Methods: Besides analyzing human publicly available dataset, we used quantitative real-time PCR, western blotting and immunohistochemistry to evaluate the expression of MNK1 in BCa and the adjacent normal bladder epithelial tissues. In vitro and in vivo proliferation assays including cell counting kit-8 and xenograft assay were carried out to explore the role of MNK1 in BCa. Chi-square test and Cox proportional hazards regression model were performed to describe MNK1's clinical significance in BCa patients.

Results: Compared to normal bladder epithelia, MNK1 was down-regulated in the clinical tumor specimens and cell lines of BCa both at mRNA and protein level. MNK1 expression was found significantly associated with advanced T status and poor overall survival (OS) of BCa patients who had received radical cystectomy and was an independent prognostic biomarker for OS. Biological function assays demonstrated that MNK1 could impair the proliferation capacities of BCa cell lines both in vivo and in vitro.

Conclusions: Unlike other cancers, MNK1 is low-expressed in BCa tissues and could inhibit the proliferation ability of BCa cells, which suggests that MNK1 might play as a tumor suppressor in BCa.

Keywords: MAP kinase-interacting kinase 1 (MNK1); bladder cancer (BCa); prognosis; proliferation; suppressor gene.