Department of Clinical Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Immunology, Faculty of Medicine, Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
Iran J Allergy Asthma Immunol. 2020 Dec 19;19(6):612-623. doi: 10.18502/ijaai.v19i6.4930.
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.
miRNAs(miRNA 或 MIR)作为治疗分子的潜在作用已将它们从基础研究转移到癌症治疗领域。先前已经表明,前列腺癌(PC)中 miR-93 的高表达和 miR-34a 的低表达,雄激素受体(AR)和前列腺特异性抗原(PSA)在这种癌症的发生和发展中起关键作用。因此,本研究旨在探讨转染和共转染 miR-34a 模拟物和 miR-93 抑制剂以及表没食子儿茶素没食子酸酯(EGCG)对前列腺癌细胞系的影响,并评估它们对 AR、PSA 表达的影响。用 miR-34a 模拟物或/和 miR-93 抑制剂以及 EGCG 处理人淋巴结前列腺癌细胞(LNCaP)。通过实时 PCR 或裂解物的 Western 印迹评估基因或蛋白表达。与对照组相比,miR-34a 模拟物的转染显着降低了 AR(p=0.0016)和 PSA(p=0.038)的 mRNA 表达。此外,miR-93 抑制剂导致 AR(p=0.0057)和 PSA(p>0.05)的 mRNA 表达与对照组相比降低。此外,与没有 EGCG 的共转染相比,与 EGCG 一起共转染导致 AR(p<0.001)和 PSA(p=0.003)的表达进一步降低。我们的研究表明,PC 细胞中 AR 和 PSA 的表达减少,然后用 miR-34a 模拟物和 miR-93 抑制剂及其与 EGCG 的组合作为天然物质进行治疗,可能是控制这些恶性细胞生长的一种有前途的治疗方法。