Elevated miR-615-3p Expression Predicts Adverse Clinical Outcome and Promotes Proliferation and Migration of Prostate Cancer Cells
Elevated miR-615-3p Expression Predicts Adverse Clinical Outcome and Promotes Proliferation and Migration of Prostate Cancer Cells
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DOI：
10.1016/j.ajpath.2019.08.007
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发表时间：
2019-12-01
影响因子：
6
通讯作者：
Sorensen, Karina D.
中科院分区：
文献类型：
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作者：
Laursen, Emma B.;Fredsoe, Jacob;Sorensen, Karina D.
与非恶性对照相比，miR-615- 3 p先前已被描述为在前列腺癌（PC）组织样本中上调;然而，其在PC中的预后潜力和功能作用在很大程度上仍未知。在这项研究中，我们研究了miR-615- 3 p在PC中的临床和生物学相关性。在239例接受根治性前列腺切除术（RP）的男性PC组织标本中测量miR-615- 3 p的表达，并研究miR-615- 3 p是否可以预测术后生化复发（BCR）。这些发现随后在三个独立的RP队列（n = 222，n = 273和n = 387）和PC细胞（PC 3 M）中进行的功能性过表达研究中得到验证。在4个独立的PC患者队列中，高miR-615- 3 p表达与BCR显著相关（P < 0.05，对数秩检验）。此外，在合并的RP队列（n = 734）中，校正前列腺癌术后风险评估（CAPRA-S）列线图后，在单变量（风险比，3.75; P < 0.001）和多变量（风险比，2.66; P = 0.008）分析中，高miR-615- 3 p表达是PC特异性生存期的显著预测因子。此外，PC细胞（PC 3 M）中miR-615- 3 p的过表达显著增加了细胞活力、增殖、凋亡和迁移。总之，我们的研究结果表明，miR-615- 3 p是术后BCR和PC特异性生存的重要预测因子，并在PC细胞中具有致癌功能。
miR-615-3p has previously been described as up-regulated in prostate cancer (PC) tissue samples compared with nonmalignant controls; however, its prognostic potential and functional role in PC remain largely unknown. In this study, we investigated the clinical and biological relevance of miR-615-3p in PC. The expression of miR-615-3p was measured in PC tissue specimens from 239 men who underwent radical prostatectomy (RP), and it was investigated if miR-615-3p could predict postoperative biochemical recurrence (BCR). These findings were subsequently validated in three independent RP cohorts (n = 222, n = 273, and n = 387) and functional overexpression studies conducted in PC cells (PC3M). High miR-615-3p expression was significantly associated with BCR in four independent PC patient cohorts (P < 0.05, log-rank test). In addition, high miR-615-3p expression was a significant predictor of PC-specific survival in univariate (hazard ratio, 3.75; P < 0.001) and multivariate (hazard ratio, 2.66; P = 0.008) analysis after adjustment for the Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) nomogram in a merged RP cohort (n = 734). Moreover, overexpression of miR-615-3p in PC cells (PC3M) significantly increased cell viability, proliferation, apoptosis, and migration. Together, our results suggest that miR-615-3p is a significant predictor of postoperative BCR and PC-specific survival and has oncogenic functions in PC cells.