miR-539 inhibits prostate cancer progression by directly targeting SPAG5.
miR-539 inhibits prostate cancer progression by directly targeting SPAG5.
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miR-539通过直接靶向SPAG5抑制前列腺癌进展
DOI：
10.1186/s13046-016-0337-8
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发表时间：
2016-04-01
期刊：
影响因子：
--
通讯作者：
Xu Y
中科院分区：
文献类型：
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作者：
Zhang H;Li S;Yang X;Qiao B;Zhang Z;Xu Y
背景我们对临床和异种移植肿瘤组织进行了多个微阵列数据集分析，以寻找前列腺癌（PCa）中疾病进展驱动的癌基因。精子相关抗原5（SPAG 5）引起了我们的注意。SPAG 5是近年来发现的参与肺癌和宫颈癌进展的癌基因。方法采用免疫组织化学方法检测SPAG 5在原发性PCa、转移性PCa、去势抵抗性PCa、神经内分泌性PCa和正常前列腺组织中的表达。我们使用患者来源的组织建立了多种体内异种移植模型，并研究了SPAG 5在这些模型中的表达趋势。我们还研究了SPAG 5在体内和体外研究中的功能。结果SPAG 5表达在PCa进展过程中逐渐增加，其表达水平与淋巴结转移、临床分期、Gleason评分和生化复发显著相关。我们的研究结果表明，SPAG 5基因敲低可以显著抑制PCa细胞的增殖，迁移和体外侵袭，并抑制肿瘤的生长和转移在体内。我们发现miR-539可以直接靶向SPAG 5。miR-539/SPAG 5在PCa中的表达受miR-539的调控，提示miR-539/SPAG 5可作为潜在的治疗靶点。
BackgroundWe conducted multiple microarray datasets analyses from clinical and xenograft tumor tissues to search for disease progression-driving oncogenes in prostate cancer (PCa). Sperm-associated antigen 5 (SPAG5) attracted our attention. SPAG5 was recently identified as an oncogene participating in lung cancer and cervical cancer progression. However, the roles of SPAG5 in PCa progression remain unknown.MethodsSPAG5 expression level in clinical primary PCa, metastatic PCa, castration resistant PCa, neuroendocrine PCa, and normal prostate tissues was investigated. We established multiple in vivo xenografts models using patient-derived tissues and investigated SPAG5 expression trend in these models. We also investigated the functions of SPAG5 in vivo and in vitro studies. Luciferase reporter assays were performed to investigate potential miRNAs that can regulate SPAG5.ResultsWe identified that SPAG5 expression was gradually increased in PCa progression and its level was significantly associated with lymph node metastasis, clinical stage, Gleason score, and biochemical recurrence. Our results indicated that SPAG5 knockdown can drastically inhibit PCa cell proliferation, migration, and invasion in vitro and supress tumor growth and metastasis in vivo. We identified that miR-539 can directly target SPAG5. Ectopic overexpression of miR-539 can drastically inhibit SPAG5 expression and the restoration of SPAG5 expression can reverse the inhibitory effects of miR-539 on PCa cell proliferation and metastasis.ConclusionOur results collectively showed a progression-driving role of SPAG5 in PCa which can be regulated by miR-539, suggesting that miR-539/SPAG5 can serve as a potential therapeutic target for PCa.