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B-cell receptor-associated protein 31 (BAP31) has been shown to overexpress in a wide range type of cancers. The present study aims to investigate the role of BAP31 on migration in lung cancer. Results showed that the migration of BAP31 knockdown cells was weaken than the control cells. Applying TGFβ to treat BAP31 knockdown cells could reduce cell migration. The enhancement on proliferation by TGFβ treatment was downregulated after BAP31 knockdown. The cell death and G0/G1 phase arrest was increased in the cells with TGFβ and BAP31 siRNA treatment when compared with TGFβ treatment alone. Gene expression analysis showed that Bax/Bcl2, MLKL and LC3 was upregulated in the cells with combinatorial treatment of TGFβ and BAP31 siRNA. In addition, BAP31 was shown to regulate multiple signaling pathways, especially for Wnt signaling. It found that BAP31 knockdown cells treated with TGFβ decreased β-catenin cytosolic expression and nuclear localization. Wnt signaling activator BIO could restore the downregulation of proliferation by BAP31 knockdown. This finding suggested that BAP31 regulated cancer cell migration is possibly involved with cell death mechanisms and Wnt signaling.

Magnesium, the second most predominant intracellular cation, plays a crucial role in many physiological functions; magnesium-based biomaterials have been widely used in clinical application. In a variety of cancer types, the high intracellular concentration of magnesium contributes to cancer initiation and progression. Therefore, we initiated this study to investigate the likelihood of confounding magnesium with cancer therapy. In this study, the anti-tumor activity of magnesium and underlying mechanisms were assessed in bladder cancer both in vitro and in vivo. The results indicated that the proliferation of bladder cancer cells was inhibited by treatment with a high concentration of MgCl2 or MgSO4. The apoptosis, G0/G1 cell cycle arrest, autophagy, and ER stress were promoted following treatment with MgCl2. However, the migratory ability of MgCl2 treated cells was similar to that of control cells, as revealed by the trans-well assay. Besides, no significant difference was observed in the proportion of CD44 or CD133 positive cells between the control and MgCl2 treated cells. Thus, to improve the therapeutic effect of magnesium, VPA was used to treat cancer cells in combination with MgCl2. As expected, combination treatment with MgCl2 and VPA could markedly reduce proliferation, migration, and in vivo tumorigenicity of UC3 cells. Moreover, the Wnt signaling was down-regulated, and ERK signaling was activated in the cells treated with combination treatment. In conclusion, the accurate utilization of MgCl2 in targeting autophagy might be beneficial in cancer therapy. Although further studies are warranted, the combination treatment of MgCl2 with VPA is an effective strategy to improve the outcome of chemotherapy.