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miR-182/PDCD4轴在非裔美国人前列腺癌侵袭性中的作用

Role of miR-182/PDCD4 axis in aggressive behavior of prostate cancer in the African Americans.

作者信息

Shiina Marisa, Hashimoto Yutaka, Kulkarni Priyanka, Dasgupta Pritha, Shahryari Varahram, Yamamura Soichiro, Tanaka Yuichiro, Dahiya Rajvir

机构信息

Department of Urology, Urology Research Center, Veterans Affairs Medical Center and University of California San Francisco School of Medicine (UCSF), 4150 Clement Street, San Francisco, CA, 94121, USA.

出版信息

BMC Cancer. 2021 Sep 15;21(1):1028. doi: 10.1186/s12885-021-08723-6.

DOI:10.1186/s12885-021-08723-6
PMID:34525952
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8444584/
Abstract

BACKGROUND

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

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。微小RNA（miRNA）在这些肿瘤中起关键作用，导致肿瘤进展。在本研究中，我们调查了miR-182在前列腺癌种族差异中的作用。

结果

我们发现与良性前列腺增生（BPH）相比，前列腺癌组织中miR-182的水平显著升高。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。我们对AA和EA患者进行了无生化复发（BCR）生存时间分析，发现高miR-182表达患者的无BCR生存时间明显短于低miR-182表达患者（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、细胞周期停滞以及集落形成受到抑制，且程度大于EA细胞系。

结论

我们的结果表明，PDCD4是miR-182的直接靶点，其抑制与AA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，且miR-182可能是AA患者有效治疗的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd97/8444584/c97f93614c5a/12885_2021_8723_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd97/8444584/b76784e9a885/12885_2021_8723_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd97/8444584/ffca58220625/12885_2021_8723_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd97/8444584/0deb0815804e/12885_2021_8723_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd97/8444584/75067921c4fc/12885_2021_8723_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd97/8444584/c97f93614c5a/12885_2021_8723_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd97/8444584/b76784e9a885/12885_2021_8723_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd97/8444584/ffca58220625/12885_2021_8723_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd97/8444584/0deb0815804e/12885_2021_8723_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd97/8444584/75067921c4fc/12885_2021_8723_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd97/8444584/c97f93614c5a/12885_2021_8723_Fig5_HTML.jpg

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