Elevation of SHARPIN Protein Levels in Prostate Adenocarcinomas Promotes Metastasis and Impairs Patient Survivals
Elevation of SHARPIN Protein Levels in Prostate Adenocarcinomas Promotes Metastasis and Impairs Patient Survivals
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前列腺腺癌中 SHARPIN 蛋白水平的升高促进转移并损害患者生存
DOI：
10.1002/pros.23302
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发表时间：
2017-05-15
期刊：
影响因子：
2.8
通讯作者：
Guo, Zhenghui
中科院分区：
文献类型：
--
作者：
Huang, Hai;Du, Tao;Guo, Zhenghui
背景。SHARPIN， shank相关RH结构域相互作用蛋白，与线性泛素链组装复合物（LUBAC）相关，调节炎症和免疫。据报道，SHARPIN在包括卵巢癌和肝癌在内的几种人类肿瘤中高表达。我们发现SHARPIN在前列腺癌细胞DU145、LNCAP和PC-3中也有高表达。在NOD/SCID小鼠模型中，SHARPIN的抑制可抑制NF-kB信号，降低培养细胞的肿瘤发生。SHARPIN在前列腺癌细胞中的过表达通过NF-kB/ERK/Akt通路和凋亡相关蛋白促进细胞生长，减少细胞凋亡。我们分析了SHARPIN在95例前列腺癌患者组织中的表达及其与前列腺癌恶性肿瘤及患者生存相关的其他临床特征的关系，并检测了siRNA抑制SHARPIN对裸鼠前列腺癌细胞增殖、血管生成、侵袭、MMP-9表达水平及肺转移的影响。高水平的SHARPIN与PCA的高恶性肿瘤相关，并预测PCA患者的生存时间较短。SHARPIN的抑制抑制了前列腺癌细胞的增殖、血管生成和侵袭，降低了前列腺癌细胞中MMP-9的水平，减少了这些细胞诱导的转移性肺肿瘤的大小。SHARPIN促进前列腺癌转移，影响患者生存。(C) 2017 Wiley期刊公司
BACKGROUND. SHARPIN, SHANK-associated RH domain interacting protein, associates with a linear ubiquitin chain assembly complex (LUBAC) to regulate inflammation and immunity. It has been reported that SHARPIN is highly expressed in several human tumors including ovarian cancer and liver cancer. We found that SHARPIN is also highly expressed in prostate cancer cell lines of DU145, LNCAP, and PC-3. Suppression of SHARPIN caused an inhibition of NF-kB signal and decreases in tumorigenesis of cultured cells in NOD/SCID mouse model. Overexpression of SHARPIN in prostate cancer cells promoted cell growth and reduced apoptosis through NF-kB/ERK/Akt pathway and apoptosis-associated proteins.METHODS. We analyzed the expression of SHARPIN in prostate cancer tissues from 95 patients and its relationship with other clinical characteristics associated with PCA malignancies and patient survivals, and examined the impacts of SHARPIN suppression with siRNA on proliferation, angiogenesis, invasion, and expression levels of MMP-9 of prostate cancer cells and metastasis to lung by these cells in nude mice.RESULTS. High levels of SHARPIN were associated with high malignancies of PCA and predicted shorter survivals of PCA patients. Suppression of SHARPIN impaired cell proliferation, angiogenesis, and invasion and reduced levels of MMP-9 in prostate cancer cells and reduced the size of metastatic lung tumors induced by these cells in mice.CONCLUSIONS. SHARPIN enhances the metastasis of prostate cancer and impair patient survivals. (C) 2017 Wiley Periodicals, Inc.