Androgen receptor regulated microRNA miR-182-5p promotes prostate cancer progression by targeting the ARRDC3/ITGB4 pathway
Androgen receptor regulated microRNA miR-182-5p promotes prostate cancer progression by targeting the ARRDC3/ITGB4 pathway
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DOI：
10.1016/j.bbrc.2016.04.107
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发表时间：
2016-05-20
影响因子：
3.1
通讯作者：
Sun, Yinghao
中科院分区：
文献类型：
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作者：
Yao, Jingjing;Xu, Chen;Sun, Yinghao
MicroRNA (miRNA) 是重要的内源性基因调节因子，在前列腺癌的发生和转移中发挥着关键作用。然而，中国患者前列腺癌组织中特定的 miRNA 表达模式仍然很大程度上未知。在本研究中，我们通过RNA测序比较了65对前列腺癌和癌旁组织中的miRNA表达模式，发现miR-182-5p是前列腺癌组织中上调最多的miRNA。该结果在 18 对前列腺癌和癌旁组织中使用实时 PCR 进行了验证。体外分析证实miR-182-5p促进前列腺癌细胞增殖、侵袭和迁移并抑制细胞凋亡。此外，雄激素受体直接调控miR-182-Sp的转录，其可以靶向ARRDC3 mRNA的3'UTR并影响ARRDC3及其下游基因ITGB4的表达。在体内实验中，miR-182-5p过表达还促进了前列腺癌肿瘤的生长和进展。在这方面，我们认为miR-182-5p可能是促进中国前列腺癌发生和转移的关键雄激素受体调节因子，并可能成为前列腺癌早期诊断和治疗研究的潜在靶点。 (C) 2016 Elsevier Inc. 保留所有权利。
MicroRNAs (miRNAs) are important endogenous gene regulators that play key roles in prostate cancer development and metastasis. However, specific miRNA expression patterns in prostate cancer tissues from Chinese patients remain largely unknown. In this study, we compared miRNA expression patterns in 65 pairs of prostate cancer and para-cancer tissues by RNA sequencing and found that miR-182-5p was the most up-regulated miRNA in prostate cancer tissues. The result was validated using realtime PCR in 18 pairs of prostate cancer and para-cancer tissues. In in vitro analysis, it was confirmed that miR-182-5p promotes prostate cancer cell proliferation, invasion and migration and inhibit apoptosis. In addition, the androgen receptor directly regulated the transcription of miR-182-Sp, which could target to the 3'UTR of ARRDC3 mRNA and affect the expression of ARRDC3 and its downstream gene ITGB4. For the in vivo experiment, miR-182-5p overexpression also promoted the growth and progression of prostate cancer tumors. In this regard, we suggest that miR-182-5p may be a key androgen receptor-regulated factor that contributes to the development and metastasis of Chinese prostate cancers and may be a potential target for the early diagnosis and therapeutic studies of prostate cancer. (C) 2016 Elsevier Inc. All rights reserved.