microRNA-183-3p Inhibits Progression of Human Prostate Cancer by Downregulating High-Mobility Group Nucleosome Binding Domain 5
microRNA-183-3p Inhibits Progression of Human Prostate Cancer by Downregulating High-Mobility Group Nucleosome Binding Domain 5
复制标题
microRNA-183-3p 通过下调高迁移率组核小体结合域 5 抑制人前列腺癌的进展
DOI：
10.1089/dna.2019.4642
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发表时间：
2019
影响因子：
3.1
通讯作者：
Zhou Liqun
中科院分区：
文献类型：
--
作者：
Li Yifan;He Shiming;Zhan Yonghao;He Anbang;Gong Yanqing;Ji Guangjie;Huang Cong;Peng Ding;Guan Bao;Li Xuesong;Zhou Liqun
microRNA是一类在癌症进展中起重要作用的非编码RNA。microRNA-183- 3 p（miR-183- 3 p）是一种在多种癌症中表达异常的新型microRNA。我们以前的研究发现高迁移率族核小体结合域5（HMGN 5）在前列腺癌中的高表达和肿瘤学作用。在这项研究中，我们发现miR-183- 3 p在前列腺癌细胞和原发组织中与正常对照相比下调。此外，miR-183- 3 p表达与HMGN 5表达呈负相关。在生物信息学预测和定量PCR及Western blot验证的基础上，证明miR-183- 3 p调控HMGN 5的表达。荧光素酶报告基因检测证实miR-183- 3 p直接靶向HMGN 5的3′-非翻译区。有趣的是，在miR-183- 3 p转染的人前列腺癌VCap和C4-2细胞中也观察到细胞增殖和迁移抑制以及凋亡诱导。HMGN 5的过表达可显著逆转miR-183- 3 p对细胞增殖和迁移的抑制作用，促进细胞凋亡。我们的数据表明，miR-183- 3 p-HMGN 5轴功能障碍发挥致癌作用，并可能成为前列腺癌的治疗靶点。
microRNAs are a class of noncoding RNAs that play important roles in cancer progression. microRNA-183-3p (miR-183-3p) is a novel microRNA that is dysregulated in many kinds of cancers. Our previous studies found high expression and oncologic role of high-mobility group nucleosome binding domain 5 (HMGN5) in prostate cancer. In this study, we found that miR-183-3p was downregulated in prostate cancer cells and primary tissues compared with normal controls. In addition, miR-183-3p expression was negatively correlated withHMGN5expression. On the basis of bioinformatics predication and quantitative polymerase chain reaction and Western blot verification, it is demonstrated that miR-183-3p regulatedHMGN5expression. Luciferase reporter assay confirmed that miR-183-3p directly targeted the 3′-untranslated region ofHMGN5. Interestingly, cell proliferation and migration inhibition and apoptosis induction were also observed in miR-183-3p transfected human prostate cancer VCap and C4-2 cells. Moreover, overexpression ofHMGN5significantly reversed the inhibitory effect on cell proliferation and migration and promoted effect on cell apoptosis by miR-183-3p. Our data suggest that dysfunction of miR-183-3p–HMGN5axis plays an oncogenic role and can be a therapeutic target for prostate cancer.