Adenylate kinase 4 promotes bladder cancer cell proliferation and invasion
Bladder cancer is the second most common urological cancer worldwide with low early diagnosis and high mortality. Since the time of diagnosis directly affects survival rate, early detection and precise biomarkers of bladder cancer are very important. Adenylate kinase 4 (AK4) is a key enzyme involved in cellular metabolism and multiple cancer development; however, the potential role of AK4 in bladder tumorigenesis is still unclear. Immunohistochemistry assay was conducted to evaluate the expression level of AK4 in 107 human bladder cancer tissues. Overall survival and recurrence-free survival were used to assess the prognosis of patients. Colony formation and MTT assays [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide] were performed to measure the proliferation capacity of tumor cells. Cell scratch assays and transwell assays were performed to measure the invasion capacity of tumor cells. The expression level of involved genes was measured by reverse transcription-polymerase chain reaction and western blot assays. The animal model was used to examine the effects of indicated protein on tumorigenesis and invasion in vivo. Herein, our study demonstrated that increased AK4 expression in patients with bladder cancer was associated with a poor prognosis. We further found that inhibition of AK4 in bladder cancer cell line T24 and 5637 can obviously inhibit the proliferation of cancer cells. Transwell assay results showed that down-regulated AK4 was related to the decreased metastasis of T24 and 5637 cells. In addition, AK4-shRNA transfected obviously inhibited tumor growth and metastasis in mice compared with the scramble group. Taken together, the results provide strong evidence of the involvement of AK4 in the progression of bladder cancer and suggest that it could have high potential as a therapeutic target of disease.
KeywordsAK4 Bladder cancer Proliferation Invasion Therapeutic target
Adenylate kinase 4
Proliferating cell nuclear antigen
Real-time quantificational polymerase chain reaction
Fetal bovine serum
FX and X-DL carried out the experiment and drafted the manuscript. D-WY and LF participated in the design of the study and performed the statistical analysis. J-HL and X-DL participated in its design and coordination and helped to draft the manuscript. All authors have read and approved the final manuscript.
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Conflict of interest
The authors declare that they have no conflict of interest.
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All of the authors have agreed to publish this article in your journal if it is accepted.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (include name of committee + reference number) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
Informed consent was obtained from all individual participants included in the study.
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