Overexpression of UNC5B in bladder cancer cells inhibits proliferation and reduces the volume of transplantation tumors in nude mice

Abstract

BackgroundThe netrin-1 receptor UNC5B plays vital roles in angiogenesis, inflammation, embryonic development and carcinogenesis. However, the functional significance of UNC5B overexpression in bladder cancer remains unclear. In this study, we investigated the role of UNC5B in bladder cancer in vitro and in vivo.MethodsStable transfection of the human bladder cancer cell line 5637 with UNC5B (5637-U) was confirmed by real-time RT-PCR, western blot and immunofluorescence assays. UNC5B expression in 5637 and 5637-U cells and mice tumor specimens derived from these cell lines was analyzed by immunohistochemistryand western blotting. Changes in the levels of cell cycle proteins were evaluated by western blotting. Flow cytometry, CCK-8 and scratch tests were used to examine cell cycle distribution, proliferation and migration, respectively.ResultsUNC5B overexpression in 5637 cells inhibited cell multiplication and migration and induced cell cycle arrest at the G2/M phase, meanwhile exhibited changes in the expression of cell cycle-associated proteins, showing that UNC5B may inhibit metastatic behaviors in bladder cancer cells. In addition, tumors generated from 5637-U cells were smaller than tumors generated from control 5637 cells.ConclusionsOur findings suggest that UNC5B is a potential anti-neoplastic target in bladder cancer progression.

Statistical and Bioinformatic Analysis of Hemimethylation Patterns in Lung Cancer

“…We can see that if a hub gene like MAPK1 is hemimethylated, it may interact with dozens of other genes. Some of these genes, e.g., EGR1 [31][32][33][34] and UNC5B [35][36][37][38], are known to be associated with cancer. Figure 5 shows genetic interactions between genes with the most hemimethylation in normal DNA, and these genes are recorded in Table 10.…”

A Cell Proliferation and Inflammatory Signature is Induced by Lawsonia intracellularis Infection in Swine

“…This gene encodes a transmembrane receptor that can regulate cell fate as a “dependence receptor” and induces apoptosis in the absence of its ligand (56, 57). Higher expression of UNC5B can inhibit cellular proliferation in some cancer cell lines and this protein is inactive and down regulated in colorectal cancer (56, 58, 59). Additionally, increased expression of UNC5B in leukocytes has been shown to attenuate inflammation (60).…”

Tumor-suppressive function of UNC5D in papillary thyroid cancer

“…In addition, one Netrin-1 receptor DCC induced G2-M arrest by inhibition of Cdk1 [ 39 ]. Most recently, UNC5B was reported to inhibit proliferation and migration by inhibiting cell cycle progression at the G2-M phase in bladder cancer cells [ 40 ]. Further studies will test whether cell-cycle arrest is a common event initiated by UNC5 receptors.…”