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

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

doi:10.1186/s12885-021-08723-6

Marisa Shiina, Soichiro Yamamura + Show 6 more

Open Access

https://doi.org/10.1186/s12885-021-08723-6

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Abstract

BackgroundProstate 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.ResultsWe 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.ConclusionsOur 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.

Highlights

Prostate cancer is the second leading cause of cancer death in men with an estimated 33,330 deaths in 2020 [1]
MicroRNAs are small non-coding regulatory RNAs of 18–24 nucleotides in length which bind to complementary sequences of mRNA, regulating post-transcriptional gene expression, and playing a pivotal role in tumorigenesis. miRNAs have been tested as potential biomarkers in cancer research [9,10,11]. miR-182, together with miR-183 and miR-96, belong to a miRNA cluster located on chromosome 7q31–34 and share similar seed sequences [12]. miR-182 is shown to be a cancer-related oncogenic miRNA that is dysregulated in Shiina et al BMC Cancer (2021) 21:1028 various cancer tissues, including breast, lung, skin, ovarian, prostate, brain, and colorectal cancers [12,13,14,15]
Diagnostic potential of miR-182 expression in prostate cancer To determine the role of miR-182 in prostate cancer, we first determined the miR-182 expression by quantitative real-time RT-PCR in benign prostatic hyperplasia (BPH) (n = 24) and prostate cancer patient samples (n = 82) from the San Francisco Veterans Affairs Medical Center (SFVAMC) cohort

Summary

Introduction

Prostate cancer is the second leading cause of cancer death in men with an estimated 33,330 deaths in 2020 [1]. African Americans (AA) have a 74% higher incidence of developing prostate cancer and are more than twice as likely to die of the disease than European American (EA) men [2, 3]. It is known that socioeconomic, educational, cultural, access to health care, and genetic factors contribute to racial disparities in prostate cancer incidence and outcome [4,5,6]. A major challenge in prostate cancer treatment is the lack of effective biomarkers. African Americans (AA) are at an increased risk of developing prostate cancer compared to European Americans (EA). We investigated the role of miR-182 in racial disparity in prostate cancer

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