ARRDC4 and UBXN1: Novel Target Genes Correlated with Prostate Cancer Gleason Score

Author:

Oh Jong Jin,Ho Jin-Nyoung,Byun Seok-Soo

Abstract

To investigate potential markers of the prostate cancer (PCa) Gleason score (GS), genetic arrays in 841 PCa patients were conducted followed by functional validation in PCa cell lines. A total of 841 PCa patients who received radical prostatectomy (RP) from November 2003 to July 2019 were enrolled. HumanExome BeadChip 12v1-1 (Illumina, Inc.; San Diego, CA, USA) exomic arrays were performed on RP tissue samples. Unconditional logistic regression was used to calculate odds ratios to generate estimates of the relative risk of pathologic GS (≥8); SNPs with the highest association were selected and validated using PCa cell lines (PC3, LNCaP, 22Rv1 and DU145). Following transfection with target-gene siRNA, assays for cell viability, wound healing, and transwell invasion were performed. Mean age of enrolled subjects was 66.34 years and median PSA was 8.43 ng/mL. After RP, 122 patients (14.5%) had pathological Gleason scores ≥8. The results from genotyping with 242,186 SNPs by exomic array revealed that 4 SNPs (rs200944490, rs117555780, rs34625170, and rs61754877) were significantly associated with high pathological GS (≥8) within cut-off level to p < 10−5. The most highly associated rs200944490 in ARRDC4 (p = 1.39 × 10−6) and rs117555780 in UBXN1 (p = 2.92 × 10−5) were selected for further validation. The knockdown of UBXN1 and ARRDC4 led to significantly reduced cell proliferation and suppressed migration and invasiveness in PCa cell lines. Epithelial mesenchymal transition (EMT) markers were significantly down-regulated in si-ARRDC4 and si-UBXN1-transfected cells. The expression levels of PI3K-phosphorylation and Akt phosphorylation and NF-κB were also suppressed following knockdown of UBXN1 and ARRDC4. The rs200944490 (ARRDC4) and rs117555780 (UBXN1) were identified as candidate markers predictive of PCa Gleason score which is strongly associated with cancer aggressiveness. Additional validation in future studies is warranted.

Funder

Seoul National University Bundang Hospital (SNUBH) Research Fund

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3