Study Of Influence And Mechanism Of Transient Receptor Potential M7 On Bladder Cancer

Objective Transient receptor potential melastatin 7（TRPM7）functions as a Mg²⁺/Ca²⁺-permeable channel fused with a kinase domain and regulates various physical processes and diseases.However,its effects on pathogenesis of human bladder cancer（BCa）has not been clarifed yet.In this study,we aim to investigate the mechanism of TRPM7 in BCa tumorigenesis by using bladder tissues,BCa cell lines and NOD-SCID mice.Method A microarray analysis using BCa tissues compared with normal bladder epithelium tissues was established to screen significantly differentially expressed genes,function and signaling pathway.qRT-PCR and immunofluorescence were used to detect the transcriptional and translational level of TRPM7 and its correlation with Epithelial-Mesenchymal Transition（EMT）markers in bladder tissues.Then we investigated the influence of TRPM7 on BCa cells via transfection with specific siRNA and overexpression-plasmid,as well as the mechanism through a rescue study by using U0126.At last,the TRPM7 inhibitor Carvacrol and stably infected cell lines were used to measure the role of TRPM7 on BCa tumorigenesis in vivo.Results Our microarray analysis has suggested that calcium signaling pathway is connected with bladder cancer via MAPK pathway.We observed increased TRPM7 expression and dysregulation of proteins involved in Epithelial-Mesenchymal Transition（EMT）in BCa tissues.Moreover,knockdown of TRPM7 in BCa cells reversed the EMT status,accompanied by increase of reactive oxygen species（ROS）.Furthermore,TRPM7 defciency could inhibit BCa cell proliferation,migration and invasion,as well as induce p-ERX1/2 and suppress the activity of PI3K/AKT.Downregulation of TRPM7 promoted cell cycle arrest at G0/G1 phase and apoptosis in vitro,which could be recovered by pre-treatment with U0126 to deactivate ERK1/2,suggesting a close correlation between TRPM7 and the MAPK signaling pathway.Furthermore,a NOD/SCID mouse model transplanted using the BCa cells was established,revealing delayed tumor growth by reduced protein activity and mRNA transcription of TRPM7 in vivo.Conclusion TRPM7 was upregulated in BCa tissues and correlated with EMT markers.TRPM7 regulate proliferation,migration and apoptosis in BCa cells through MAPK signaling pathway triggered by Ca²⁺ homeostasis dysregulation.