The microRNA miR-3174 Suppresses the Expression of ADAM15 and Inhibits the Proliferation of Patient-Derived Bladder Cancer Cells

Chunhu Yu,1 Ying Wang,1 Tiejun Liu,1 Kefu Sha,1 Zhaoxia Song,1 Mingjun Zhao,1 Xiaolin Wang2 1Department of Urinary Surgery, Beijing Rehabilitation Hospital of Capital Medical University, Beijing 100144, People’s Republic of China; 2The Third District of Airforce Special Service Sanatorium, Chinese People’s Liberation Army Air Force, Hangzhou 310021, Zhejiang Province, People’s Republic of ChinaCorrespondence: Xiaolin Wang Email xiaolin_wang2019@sina.comBackground: Bladder cancer is a major urinary system cancer, and its mechanism of action regarding its progression is unclear. The goal of this study was to examine the expression of ADAM panel in the clinical specimens of bladder cancer and to investigate the role of miR-3174/ADAM15 (a disintegrin and metalloprotease 15) axis in the regulation of bladder cancer cell proliferation.Methods: The expression of an ADAM gene panel (including ADAM8, 9, 10, 11, 12, 15, 17, 19, 22, 23, 28, and 33), including 30 pairs of bladder tumor and non-tumor specimens, was examined by Ion AmpliSeq Targeted Sequencing. A microRNA (miRNA) that could potentially target the ADAM with the highest expression level in the tumor tissue was identified using the online tool miRDB. Next, the interaction between the miRNA and ADAM15 was identified by Western blot. Finally, the proliferation of bladder cancer cells was examined using MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) experiments (cell proliferation examining) and subcutaneous tumor models by using nude mice.Results: The expression of ADAM15 in tumor tissue was found statistically significant when compared to its expression in non-tumor tissue. Additionally, ADAM15’s expression in tumor tissue was found the highest of all other tested ADAMs. Next, by using the online tool miRDB, a microRNA termed miR-3174 was identified that targets ADAM15 and inhibits its expression by binding to its 3′-untranslated region. Finally, we found that overexpression of miR-3174 in bladder cancer cells inhibited the proliferation of cells due to the inhibition of ADAM15.Conclusion: In the present work, the data highlight that miR-3174 inhibits the proliferation of bladder cancer cells by targeting ADAM15.Keywords: ADAM, bladder cancer, metastasis, microRNA, proliferation