Inducing apoptosis by using microRNA in radio-resistant prostate cancer: an in-silico study with an in-vitro validation.

ABSTRACT

BACKGROUND: One of the problems with radiation therapy (RT) is that prostate tumor cells are often radio-resistant, which results in treatment failure. This study aimed to determine the procedure involved in radio-resistant prostate cancer apoptosis. For a deeper insight, we devoted a novel bioinformatics approach to analyze the targeting between microRNAs and radio-resistant prostate cancer genes. METHOD: This study uses the Tarbase, and the Mirtarbase databases as validated experimental databases and mirDIP as a predicted database to identify microRNAs that target radio-resistant anti-apoptotic genes. These genes are used to construct the radio-resistant prostate cancer genes network using the online tool STRING. The validation of causing apoptosis by using microRNA was confirmed with flow cytometry of Annexin V. RESULTS: The anti-apoptotic gene of radio-resistant prostate cancer included BCL-2, MCL1, XIAP, STAT3, NOTCH1, REL, REL B, BIRC3, and AKT1 genes. These genes were identified as anti-apoptotic genes for radio-resistant prostate cancer. The crucial microRNA that knockdown all of these genes was hsa-miR-7-5p. The highest rate of apoptotic cells in a cell transfected with hsa-miR-7-5p was (32.90 ± 1.49), plenti III (21.99 ± 3.72), and the control group (5.08 ± 0.88) in 0 Gy (P < 0.001); also, this rate was in miR-7-5p (47.01 ± 2.48), plenti III (33.79 ± 3.40), and the control group (16.98 ± 3.11) (P < 0.001) for 4 Gy. CONCLUSION: The use of this new treatment such as gene therapy to suppress genes involved in apoptosis can help to improve the treatment results and increase the quality of life of patients with prostate cancer.