Loss of miR-516a-3p mediates upregulation of ABCC5 in prostate cancer and drives its progression.
Loss of miR-516a-3p mediates upregulation of ABCC5 in prostate cancer and drives its progression.
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miR-516a-3p 的缺失介导前列腺癌中 ABCCCC5 的上调并驱动其进展
DOI：
10.2147/ott.s167463
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发表时间：
2018
影响因子：
4
通讯作者：
Xu Y
中科院分区：
文献类型：
--
作者：
Zhang H;Lian Z;Sun G;Liu R;Xu Y
为了全面了解ABCC 5是否可以调节前列腺癌（PCa）的进展，我们进行了微阵列数据分析，并确定ABCC 5在原发性PCa中相对于正常样本显著增加，转移性PCa相对于原发性PCa，去势抵抗性PCa相对于激素初治PCa，分别。多变量考克斯回归分析表明，ABCC 5在PCa中的过表达是生化无复发和总生存率差的独立预后因素。我们证明ABCC 5敲低在体外显著抑制PCa细胞增殖、迁移和侵袭，并在体内抑制肿瘤生长和转移。我们还证明了miR-516 a-3 p在PCa中显著下调。我们最终证明ABCC 5是miR-516 a-3 p的直接靶点。miR-516 a-3 p过表达可以复制ABCC 5敲减诱导的表型，而ABCC 5的强制表达可以显著逆转miR-516 a-3 p的抑制作用。miR-516 a-3 p可能通过靶向ABCC 5来调节癌细胞对阿霉素和多西他赛的敏感性，这对新治疗药物的设计具有重要意义。综上所述，我们的研究结果表明，miR-516 a-3 p表达的丧失以及因此不受控制的ABCC 5上调可能驱动PCa进展并影响化疗敏感性。
To gain a comprehensive understanding of whether ABCC5 can regulate prostate cancer (PCa) progression, we performed microarray data analyses and identified that ABCC5 was drastically increased in primary PCa relative to normal samples, metastatic PCa relative to primary PCa, and castration-resistant PCa relative to hormone naïve PCa, respectively. Multivariate Cox regression analysis suggested that ABCC5 overexpression in PCa was an independent prognostic factor for both poor biochemical recurrence-free and overall survival. We demonstrated that ABCC5 knockdown significantly inhibits PCa cell proliferation, migration, and invasion in vitro and suppresses tumor growth and metastasis in vivo. We also demonstrated that miR-516a-3p was significantly downregulated in PCa. We finally demonstrated that ABCC5 was a direct target of miR-516a-3p. miR-516a-3p overexpression can phenotypically copy ABCC5 knockdown-induced phenotypes, whereas forced expression of ABCC5 can drastically reverse the inhibitory effects of miR-516a-3p. miR-516a-3p may modulate the sensitivity of cancer cells to adriamycin and docetaxel by targeting ABCC5 with important implications in the design of new therapeutic agents. Taken together, our results indicated that loss of miR-516a-3p expression and thus uncontrolled ABCC5 upregulation might drive PCa progression and influence chemosensitivity.