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Role of miR-182/PDCD4 axis in aggressive behavior of prostate cancer in the African Americans
BMC Cancer ( IF 3.4 ) Pub Date : 2021-09-15 , DOI: 10.1186/s12885-021-08723-6
Marisa Shiina 1 , Yutaka Hashimoto 1 , Priyanka Kulkarni 1 , Pritha Dasgupta 1 , Varahram Shahryari 1 , Soichiro Yamamura 1 , Yuichiro Tanaka 1 , Rajvir Dahiya 1
Affiliation  

Prostate cancer is one of the most commonly diagnosed cancers among men. African Americans (AA) are at an increased risk of developing prostate cancer compared to European Americans (EA). miRNAs play a critical role in these tumors, leading to tumor progression. In this study, we investigated the role of miR-182 in racial disparity in prostate cancer. We found significantly increased levels of miR-182 in prostate cancer tissues compared to BPH. Also, miR-182 shows increased expression in AA prostate cancer cell line and tissue samples compared to EA. We performed biochemical recurrence (BCR) - free survival time in AA and EA patients and found that high miR-182 expression had significantly shorter BCR-free survival than patients with low miR-182 expression (P = 0.031). To elucidate the role of miR-182, we knocked down miR-182 in EA (DU-145 and LNCaP) and AA (MDA-PCa-2b) cell lines and found an increase in apoptosis, arrest of the cell cycle, and inhibition of colony formation in the AA cell line to a greater extent than EA cell lines. Our results showed that PDCD4 is a direct miR-182 target and its inhibition is associated with aggressiveness and high Gleason grade in prostate cancer among AA. These findings show that miR-182 is highly expressed in AA patients and miR-182 may be a target for effective therapy in AA patients.

中文翻译:

miR-182/PDCD4 轴在非裔美国人前列腺癌侵袭行为中的作用

前列腺癌是男性中最常被诊断出的癌症之一。与欧洲裔美国人 (EA) 相比,非裔美国人 (AA) 患前列腺癌的风险更高。miRNA在这些肿瘤中发挥关键作用,导致肿瘤进展。在这项研究中,我们调查了 miR-182 在前列腺癌种族差异中的作用。我们发现与 BPH 相比,前列腺癌组织中 miR-182 的水平显着增加。此外,与 EA 相比,miR-182 在 AA 前列腺癌细胞系和组织样本中的表达增加。我们在 AA 和 EA 患者中进行了生化复发 (BCR) - 无生存时间,发现高 miR-182 表达的无 BCR 生存时间明显短于低 miR-182 表达的患者 (P = 0.031)。为了阐明 miR-182 的作用,我们在 EA(DU-145 和 LNCaP)和 AA(MDA-PCa-2b)细胞系中敲低 miR-182,发现 AA 细胞系中的细胞凋亡增加、细胞周期停滞和集落形成受到抑制比 EA 细胞系更大。我们的研究结果表明,PDCD4 是 miR-182 的直接靶标,其抑制与 AA 中前列腺癌的侵袭性和高 Gleason 分级相关。这些发现表明 miR-182 在 AA 患者中高表达,miR-182 可能是 AA 患者有效治疗的靶点。我们的研究结果表明,PDCD4 是 miR-182 的直接靶标,其抑制与 AA 中前列腺癌的侵袭性和高 Gleason 分级相关。这些发现表明 miR-182 在 AA 患者中高表达,miR-182 可能是 AA 患者有效治疗的靶点。我们的研究结果表明,PDCD4 是 miR-182 的直接靶标,其抑制与 AA 中前列腺癌的侵袭性和高 Gleason 分级相关。这些发现表明 miR-182 在 AA 患者中高表达,miR-182 可能是 AA 患者有效治疗的靶点。
更新日期:2021-09-16
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