Epigallocatechin-3-gallate Enhances the Efficacy of MicroRNA-34a Mimic and MicroRNA-93 Inhibitor Co-transfection in Prostate Cancer Cell Line
-
Hossein Mokhtari
,
Bahram Yaghmaei
,
Majid Sirati-Sabet
,
Narjes Jafari
,
Alireza Mardomi
,
Saeid Abediankenari
,
Abdolkarim Mahrooz
Abstract
The potential role of microRNAs (miRNA or MIR) as therapeutic molecules has moved them from basic research to the field of cancer therapy. High expression of miR-93 and low expression of miR-34a have previously been indicated in prostate cancer (PC), which is the second leading cause of cancer-related death in men. Androgen receptor (AR) and prostate-specific antigen (PSA) play key roles in the initiation and progression of this cancer. Therefore, this study aimed to investigate the effects of the transfection and co-transfection of miR-34a mimic and miR-93 inhibitor with or without epigallocatechin-3-gallate (EGCG) on prostate cancer cell line and also to evaluate their effects on the expression of AR, PSA. Human lymph node carcinoma of the prostate (LNCaP) cells were treated with miR-34a mimic or/and miR-93 inhibitor with or without EGCG. Gene or protein expressions were assessed by real-time PCR or western blotting of lysates. The transfection with miR-34a mimics significantly reduced the mRNA expression of AR (p=0.0016), and PSA (p=0.038) compared to the control. Also, the miR-93 inhibitor led to a decrease in the mRNA expression of AR (p=0.0057) and PSA (p>0.05) compared to the control group. Furthermore, the co-transfection, along with EGCG, caused more decrease in both the AR (p<0.001) and the PSA (p=0.003) expression compared with the co-transfection without EGCG. Our study indicates that the reduced expression of AR and PSA in PC cells followed by treatment with miR-34a mimic and miR-93 inhibitor and their combination with EGCG as a natural substance may be a promising therapeutic way for controlling the growth of these malignant cells.
1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet‐Tieulent J, Jemal A. Global cancer statistics, 2012. Ca-Cancer J Clin. 2015;65(2):87-108.
2. Cucchiara V, Yang JC, Mirone V, Gao AC, Rosenfeld MG, Evans CP. Epigenomic regulation of androgen receptor signaling: Potential role in prostate cancer therapy. Cancers. 2017;9(1):9.
3. Agoulnik IU, Krause WC, Bingman WE, Rahman HT, Amrikachi M, Ayala GE, et al. Repressors of androgen and progesterone receptor action. J Biol Chem. 2003;278(33):31136-48.
4. Culig Z, Bartsch G. Androgen axis in prostate cancer. J Cell Biochem. 2006;99(2):373-81.
5. Taichman RS, Loberg RD, Mehra R, Pienta KJ. The evolving biology and treatment of prostate cancer. J CLIN INVEST. 2007;117(9):2351-61.
6. Burnstein KL. Regulation of androgen receptor levels: implications for prostate cancer progression and therapy. J Cell Biochem. 2005;95(4):657-69.
7. Heinlein CA, Chang C. Androgen receptor (AR) coregulators: an overview. Endocr Rev. 2002;23(2):175-200.
8. Mahrooz A, Mackness M, Bagheri A, Ghaffari-Cherati M, Masoumi P. The epigenetic regulation of paraoxonase 1 (PON1) as an important enzyme in HDL function: The missing link between environmental and genetic regulation. Clin Biochem. 2019;73:1-10.
9.Takayama K-i, Misawa A, Inoue S. Significance of microRNAs in androgen signaling and prostate cancer progression. Cancers. 2017;9(8):102.
10. Filella X, Foj L. miRNAs as novel biomarkers in the management of prostate cancer. Clin Chem Lab Med. 2017;55(5):715-36.
11. Fabris L, Ceder Y, Chinnaiyan AM, Jenster GW, Sorensen KD, Tomlins S, et al. The potential of microRNAs as prostate cancer biomarkers. Eur Urol. 2016;70(2):312-22.
12. Shivdasani RA. MicroRNAs: regulators of gene expression and cell differentiation. Blood. 2006;108(12):3646-53.
13. Negrini M, Ferracin M, Sabbioni S, Croce CM. MicroRNAs in human cancer: from research to therapy. J Cell Sci. 2007;120(11):1833-40.
14. Schaefer A, Jung M, Kristiansen G, Lein M, Schrader M, Miller K, et al., editors. MicroRNAs and cancer: current state and future perspectives in urologic oncology. UROL ONCOL-SEMIN ORI; 2010: Elsevier.
15. Hanna J, Hossain GS, Kocerha J. The potential for microRNA therapeutics and clinical research. Front Genet. 2019;10:478.
16. Liu J-J, Zhang X, Wu X-H. miR-93 promotes the growth and invasion of prostate cancer by upregulating its target genes TGFBR2, ITGB8, and LATS2. Mol Ther--Oncolytics. 2018;11:14-9.
17. Li N, Miao Y, Shan Y, Liu B, Li Y, Zhao L, et al. MiR-106b and miR-93 regulate cell progression by suppression of PTEN via PI3K/Akt pathway in breast cancer. Cell Death Dis. 2017;8(5):e2796-e.
18. Misso G, Di Martino MT, De Rosa G, Farooqi AA, Lombardi A, Campani V, et al. Mir-34: a new weapon against cancer? Mol Ther--Nucleic Acids. 2014;3:e195.
19. Rokavec M, Li H, Jiang L, Hermeking H. The p53/miR-34 axis in development and disease. J Mol Cell Biol. 2014;6(3):214-30.
20. Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, et al. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med. 2011;17(2):211-5.
21. Gan R-Y, Li H-B, Sui Z-Q, Corke H. Absorption, metabolism, anti-cancer effect and molecular targets of epigallocatechin gallate (EGCG): An updated review. Crit Rev Food Sci Nutr. 2018;58(6):924-41.
22. Sen T, Dutta A, Chatterjee A. Epigallocatechin-3-gallate (EGCG) downregulates gelatinase-B (MMP-9) by involvement of FAK/ERK/NFκB and AP-1 in the human breast cancer cell line MDA-MB-231. Anti-Cancer Drugs. 2010;21(6):632-44.
23. Kumazoe M, Tachibana H. Anti-cancer effect of EGCG and its mechanisms. Funct Foods Health Dis. 2016;6(2):70-8.
24. Li Y, Yuan Y-Y, Meeran SM, Tollefsbol TO. Synergistic epigenetic reactivation of estrogen receptor-α (ERα) by combined green tea polyphenol and histone deacetylase inhibitor in ERα-negative breast cancer cells. Mol Cancer. 2010;9(1):274.
25.Brueckner B, Lyko F. DNA methyltransferase inhibitors: old and new drugs for an epigenetic cancer therapy. Trends Pharmacol Sci. 2004;25(11):551-4.
26.Zan L, Chen Q, Zhang L, Li X. Epigallocatechin gallate (EGCG) suppresses growth and tumorigenicity in breast cancer cells by downregulation of miR-25. Bioengineered. 2019;10(1):374-82.
27. Zhou H, Chen JX, Yang CS, Yang MQ, Deng Y, Wang H. Gene regulation mediated by microRNAs in response to green tea polyphenol EGCG in mouse lung cancer. BMC genomics. 2014;15(S11):S3.
28. Rokhlin OW, Scheinker VS, Taghiyev AF, Bumcrot D, Glover RA, Cohen MB. MicroRNA-34 mediates AR-dependent p53-induced apoptosis in prostate cancer. Cancer Biol Ther. 2008;7(8):1288-96.
29. Lodygin D, Tarasov V, Epanchintsev A, Berking C, Knyazeva T, Körner H, et al. Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer. Cell cycle. 2008;7(16):2591-600.
30. Toyota M, Suzuki H, Sasaki Y, Maruyama R, Imai K, Shinomura Y, et al. Epigenetic silencing of microRNA-34b/c and B-cell translocation gene 4 is associated with CpG island methylation in colorectal cancer. Cancer Res. 2008;68(11):4123-32.
31. He L, He X, Lim LP, De Stanchina E, Xuan Z, Liang Y, et al. A microRNA component of the p53 tumour suppressor network. Nature. 2007;447(7148):1130-4.
32. Choi N, Park J, Lee J-S, Yoe J, Park GY, Kim E, et al. miR-93/miR-106b/miR-375-CIC-CRABP1: a novel regulatory axis in prostate cancer progression. Oncotarget. 2015;6(27):23533.
33.Liang H, Wang F, Chu D, Zhang W, Liao Z, Fu Z, et al. miR-93 functions as an oncomiR for the downregulation of PDCD4 in gastric carcinoma. Sci Rep. 2016;6(1):1-11.
34. Fang L, Deng Z, Shatseva T, Yang J, Peng C, Du W, et al. MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-β8. Oncogene. 2011;30(7):806-21.
35. Chakrabarti M, Khandkar M, Banik NL, Ray SK. Alterations in expression of specific microRNAs by combination of 4-HPR and EGCG inhibited growth of human malignant neuroblastoma cells. Brain Res. 2012;1454:1-13.
36. Tsang WP, Kwok TT. Epigallocatechin gallate up-regulation of miR-16 and induction of apoptosis in human cancer cells. J Nutr Biochem. 2010;21(2):140-6.
37. Toden S, Tran H-M, Tovar-Camargo OA, Okugawa Y, Goel A. Epigallocatechin-3-gallate targets cancer stem-like cells and enhances 5-fluorouracil chemosensitivity in colorectal cancer. Oncotarget. 2016;7(13):16158.
38. Kress TR, Cannell IG, Brenkman AB, Samans B, Gaestel M, Roepman P, et al. The MK5/PRAK kinase and Myc form a negative feedback loop that is disrupted during colorectal tumorigenesis. Molecular cell. 2011;41(4):445-57.
39. Sotillo E, Laver T, Mellert H, Schelter J, Cleary M, McMahon S, et al. Myc overexpression brings out unexpected antiapoptotic effects of miR-34a. Oncogene. 2011;30(22):2587-94.
40. Kashat M, Azzouz L, Sarkar SH, Kong D, Li Y, Sarkar FH. Inactivation of AR and Notch-1 signaling by miR-34a attenuates prostate cancer aggressiveness. Am J Transl Res. 2012;4(4):432.
41. Heemers HV, Tindall DJ. Androgen receptor (AR) coregulators: a diversity of functions converging on and regulating the AR transcriptional complex. Endocr Rev. 2007;28(7):778-808.
42. Saxena P, Trerotola M, Wang T, Li J, Sayeed A, VanOudenhove J, et al. PSA regulates androgen receptor expression in prostate cancer cells. The Prostate. 2012;72(7):769-76.
43. Vogt M, Munding J, Grüner M, Liffers S-T, Verdoodt B, Hauk J, et al. Frequent concomitant inactivation of miR-34a and miR-34b/c by CpG methylation in colorectal, pancreatic, mammary, ovarian, urothelial, and renal cell carcinomas and soft tissue sarcomas. Virchows Arch. 2011;458(3):313-22.
44. Hu J, Yi T, Chu S, Zeng H, Xia P, Liu G, et al. DNA methylation of miR-93: an important event in acquiring drug resistance in breast cancer cells. Int J Clin Exp Med. 2019;12(5):4697-706.
45. Long MD, Smiraglia DJ, Campbell MJ. The genomic impact of DNA CpG methylation on gene expression; relationships in prostate cancer. Biomolecules. 2017;7(1):15.
46. He X-X, Kuang S-Z, Liao J-Z, Xu C-R, Chang Y, Wu Y-L, et al. The regulation of microRNA expression by DNA methylation in hepatocellular carcinoma. Mol BioSyst. 2015;11(2):532-9.
47. Singh BN, Shankar S, Srivastava RK. Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochem Pharmacol. 2011;82(12):1807-21.
48. Supic G, Jagodic M, Magic Z. Epigenetics: a new link between nutrition and cancer. Nutr Cancer. 2013;65(6):781-92.
49. Khan N, Mukhtar H. Cancer and metastasis: prevention and treatment by green tea. Cancer Metastasis Rev. 2010;29(3):435-45.
50. Sato F, Tsuchiya S, Meltzer SJ, Shimizu K. MicroRNAs and epigenetics. The FEBS journal. 2011;278(10):1598-609.
51. Sumazin P, Yang X, Chiu H-S, Chung W-J, Iyer A, Llobet-Navas D, et al. An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma. Cell. 2011;147(2):370-81.
52. Miller DM, Thomas SD, Islam A, Muench D, Sedoris K. c-Myc and cancer metabolism. AACR; 2012.
53. Hill M, Tran N. MicroRNAs regulating microRNAs in cancer. Trends Cancer. 2018;4(7):465-8.
2. Cucchiara V, Yang JC, Mirone V, Gao AC, Rosenfeld MG, Evans CP. Epigenomic regulation of androgen receptor signaling: Potential role in prostate cancer therapy. Cancers. 2017;9(1):9.
3. Agoulnik IU, Krause WC, Bingman WE, Rahman HT, Amrikachi M, Ayala GE, et al. Repressors of androgen and progesterone receptor action. J Biol Chem. 2003;278(33):31136-48.
4. Culig Z, Bartsch G. Androgen axis in prostate cancer. J Cell Biochem. 2006;99(2):373-81.
5. Taichman RS, Loberg RD, Mehra R, Pienta KJ. The evolving biology and treatment of prostate cancer. J CLIN INVEST. 2007;117(9):2351-61.
6. Burnstein KL. Regulation of androgen receptor levels: implications for prostate cancer progression and therapy. J Cell Biochem. 2005;95(4):657-69.
7. Heinlein CA, Chang C. Androgen receptor (AR) coregulators: an overview. Endocr Rev. 2002;23(2):175-200.
8. Mahrooz A, Mackness M, Bagheri A, Ghaffari-Cherati M, Masoumi P. The epigenetic regulation of paraoxonase 1 (PON1) as an important enzyme in HDL function: The missing link between environmental and genetic regulation. Clin Biochem. 2019;73:1-10.
9.Takayama K-i, Misawa A, Inoue S. Significance of microRNAs in androgen signaling and prostate cancer progression. Cancers. 2017;9(8):102.
10. Filella X, Foj L. miRNAs as novel biomarkers in the management of prostate cancer. Clin Chem Lab Med. 2017;55(5):715-36.
11. Fabris L, Ceder Y, Chinnaiyan AM, Jenster GW, Sorensen KD, Tomlins S, et al. The potential of microRNAs as prostate cancer biomarkers. Eur Urol. 2016;70(2):312-22.
12. Shivdasani RA. MicroRNAs: regulators of gene expression and cell differentiation. Blood. 2006;108(12):3646-53.
13. Negrini M, Ferracin M, Sabbioni S, Croce CM. MicroRNAs in human cancer: from research to therapy. J Cell Sci. 2007;120(11):1833-40.
14. Schaefer A, Jung M, Kristiansen G, Lein M, Schrader M, Miller K, et al., editors. MicroRNAs and cancer: current state and future perspectives in urologic oncology. UROL ONCOL-SEMIN ORI; 2010: Elsevier.
15. Hanna J, Hossain GS, Kocerha J. The potential for microRNA therapeutics and clinical research. Front Genet. 2019;10:478.
16. Liu J-J, Zhang X, Wu X-H. miR-93 promotes the growth and invasion of prostate cancer by upregulating its target genes TGFBR2, ITGB8, and LATS2. Mol Ther--Oncolytics. 2018;11:14-9.
17. Li N, Miao Y, Shan Y, Liu B, Li Y, Zhao L, et al. MiR-106b and miR-93 regulate cell progression by suppression of PTEN via PI3K/Akt pathway in breast cancer. Cell Death Dis. 2017;8(5):e2796-e.
18. Misso G, Di Martino MT, De Rosa G, Farooqi AA, Lombardi A, Campani V, et al. Mir-34: a new weapon against cancer? Mol Ther--Nucleic Acids. 2014;3:e195.
19. Rokavec M, Li H, Jiang L, Hermeking H. The p53/miR-34 axis in development and disease. J Mol Cell Biol. 2014;6(3):214-30.
20. Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, et al. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med. 2011;17(2):211-5.
21. Gan R-Y, Li H-B, Sui Z-Q, Corke H. Absorption, metabolism, anti-cancer effect and molecular targets of epigallocatechin gallate (EGCG): An updated review. Crit Rev Food Sci Nutr. 2018;58(6):924-41.
22. Sen T, Dutta A, Chatterjee A. Epigallocatechin-3-gallate (EGCG) downregulates gelatinase-B (MMP-9) by involvement of FAK/ERK/NFκB and AP-1 in the human breast cancer cell line MDA-MB-231. Anti-Cancer Drugs. 2010;21(6):632-44.
23. Kumazoe M, Tachibana H. Anti-cancer effect of EGCG and its mechanisms. Funct Foods Health Dis. 2016;6(2):70-8.
24. Li Y, Yuan Y-Y, Meeran SM, Tollefsbol TO. Synergistic epigenetic reactivation of estrogen receptor-α (ERα) by combined green tea polyphenol and histone deacetylase inhibitor in ERα-negative breast cancer cells. Mol Cancer. 2010;9(1):274.
25.Brueckner B, Lyko F. DNA methyltransferase inhibitors: old and new drugs for an epigenetic cancer therapy. Trends Pharmacol Sci. 2004;25(11):551-4.
26.Zan L, Chen Q, Zhang L, Li X. Epigallocatechin gallate (EGCG) suppresses growth and tumorigenicity in breast cancer cells by downregulation of miR-25. Bioengineered. 2019;10(1):374-82.
27. Zhou H, Chen JX, Yang CS, Yang MQ, Deng Y, Wang H. Gene regulation mediated by microRNAs in response to green tea polyphenol EGCG in mouse lung cancer. BMC genomics. 2014;15(S11):S3.
28. Rokhlin OW, Scheinker VS, Taghiyev AF, Bumcrot D, Glover RA, Cohen MB. MicroRNA-34 mediates AR-dependent p53-induced apoptosis in prostate cancer. Cancer Biol Ther. 2008;7(8):1288-96.
29. Lodygin D, Tarasov V, Epanchintsev A, Berking C, Knyazeva T, Körner H, et al. Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer. Cell cycle. 2008;7(16):2591-600.
30. Toyota M, Suzuki H, Sasaki Y, Maruyama R, Imai K, Shinomura Y, et al. Epigenetic silencing of microRNA-34b/c and B-cell translocation gene 4 is associated with CpG island methylation in colorectal cancer. Cancer Res. 2008;68(11):4123-32.
31. He L, He X, Lim LP, De Stanchina E, Xuan Z, Liang Y, et al. A microRNA component of the p53 tumour suppressor network. Nature. 2007;447(7148):1130-4.
32. Choi N, Park J, Lee J-S, Yoe J, Park GY, Kim E, et al. miR-93/miR-106b/miR-375-CIC-CRABP1: a novel regulatory axis in prostate cancer progression. Oncotarget. 2015;6(27):23533.
33.Liang H, Wang F, Chu D, Zhang W, Liao Z, Fu Z, et al. miR-93 functions as an oncomiR for the downregulation of PDCD4 in gastric carcinoma. Sci Rep. 2016;6(1):1-11.
34. Fang L, Deng Z, Shatseva T, Yang J, Peng C, Du W, et al. MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-β8. Oncogene. 2011;30(7):806-21.
35. Chakrabarti M, Khandkar M, Banik NL, Ray SK. Alterations in expression of specific microRNAs by combination of 4-HPR and EGCG inhibited growth of human malignant neuroblastoma cells. Brain Res. 2012;1454:1-13.
36. Tsang WP, Kwok TT. Epigallocatechin gallate up-regulation of miR-16 and induction of apoptosis in human cancer cells. J Nutr Biochem. 2010;21(2):140-6.
37. Toden S, Tran H-M, Tovar-Camargo OA, Okugawa Y, Goel A. Epigallocatechin-3-gallate targets cancer stem-like cells and enhances 5-fluorouracil chemosensitivity in colorectal cancer. Oncotarget. 2016;7(13):16158.
38. Kress TR, Cannell IG, Brenkman AB, Samans B, Gaestel M, Roepman P, et al. The MK5/PRAK kinase and Myc form a negative feedback loop that is disrupted during colorectal tumorigenesis. Molecular cell. 2011;41(4):445-57.
39. Sotillo E, Laver T, Mellert H, Schelter J, Cleary M, McMahon S, et al. Myc overexpression brings out unexpected antiapoptotic effects of miR-34a. Oncogene. 2011;30(22):2587-94.
40. Kashat M, Azzouz L, Sarkar SH, Kong D, Li Y, Sarkar FH. Inactivation of AR and Notch-1 signaling by miR-34a attenuates prostate cancer aggressiveness. Am J Transl Res. 2012;4(4):432.
41. Heemers HV, Tindall DJ. Androgen receptor (AR) coregulators: a diversity of functions converging on and regulating the AR transcriptional complex. Endocr Rev. 2007;28(7):778-808.
42. Saxena P, Trerotola M, Wang T, Li J, Sayeed A, VanOudenhove J, et al. PSA regulates androgen receptor expression in prostate cancer cells. The Prostate. 2012;72(7):769-76.
43. Vogt M, Munding J, Grüner M, Liffers S-T, Verdoodt B, Hauk J, et al. Frequent concomitant inactivation of miR-34a and miR-34b/c by CpG methylation in colorectal, pancreatic, mammary, ovarian, urothelial, and renal cell carcinomas and soft tissue sarcomas. Virchows Arch. 2011;458(3):313-22.
44. Hu J, Yi T, Chu S, Zeng H, Xia P, Liu G, et al. DNA methylation of miR-93: an important event in acquiring drug resistance in breast cancer cells. Int J Clin Exp Med. 2019;12(5):4697-706.
45. Long MD, Smiraglia DJ, Campbell MJ. The genomic impact of DNA CpG methylation on gene expression; relationships in prostate cancer. Biomolecules. 2017;7(1):15.
46. He X-X, Kuang S-Z, Liao J-Z, Xu C-R, Chang Y, Wu Y-L, et al. The regulation of microRNA expression by DNA methylation in hepatocellular carcinoma. Mol BioSyst. 2015;11(2):532-9.
47. Singh BN, Shankar S, Srivastava RK. Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochem Pharmacol. 2011;82(12):1807-21.
48. Supic G, Jagodic M, Magic Z. Epigenetics: a new link between nutrition and cancer. Nutr Cancer. 2013;65(6):781-92.
49. Khan N, Mukhtar H. Cancer and metastasis: prevention and treatment by green tea. Cancer Metastasis Rev. 2010;29(3):435-45.
50. Sato F, Tsuchiya S, Meltzer SJ, Shimizu K. MicroRNAs and epigenetics. The FEBS journal. 2011;278(10):1598-609.
51. Sumazin P, Yang X, Chiu H-S, Chung W-J, Iyer A, Llobet-Navas D, et al. An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma. Cell. 2011;147(2):370-81.
52. Miller DM, Thomas SD, Islam A, Muench D, Sedoris K. c-Myc and cancer metabolism. AACR; 2012.
53. Hill M, Tran N. MicroRNAs regulating microRNAs in cancer. Trends Cancer. 2018;4(7):465-8.
| Files | ||
| Issue | Vol 19 No 6 (2020) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v19i6.4930 | |
| PMID | 33463130 | |
| Keywords | ||
| Androgen receptor MicroRNAs Prostate cancer Prostate-specific antigen | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Mokhtari H, Yaghmaei B, Sirati-Sabet M, Jafari N, Mardomi A, Abediankenari S, Mahrooz A. Epigallocatechin-3-gallate Enhances the Efficacy of MicroRNA-34a Mimic and MicroRNA-93 Inhibitor Co-transfection in Prostate Cancer Cell Line. Iran J Allergy Asthma Immunol. 2020;19(6):612-623.
