sirna介导的stathmin1沉默抑制前列腺癌细胞的增殖。

Asude Aksoy, Selcen Göktürk, Ebru Etem Önalan, Ahmet Tektemur, Gökhan Artaş, Asuman Varoğlu, Mustafa Koç
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引用次数: 0

摘要

Stathmin1 (STMN1)已被提出作为一种可能的预后标志物和一些癌症的潜在治疗靶点。我们旨在分析小干扰RNA (siRNA)介导STMN1沉默后前列腺癌(PCa)细胞系(PC-3)中自噬、侵袭、凋亡相关基因的变化,以及STMN1表达、临床病理参数和前列腺癌患者生存(OS)的关系。用免疫组织化学方法分析75例前列腺癌和15例前列腺增生组织中STMN1的表达。在PCa病例中确定STMN1表达水平、临床病理特征和OS之间的相关性。转染sirna介导的STMN1孵育PC-3细胞,并与阴性对照sirna进行比较。我们采用逆转录聚合酶链反应(RT-PCR)和western blotting联合检测STMN1沉默后PC3细胞株自噬、侵袭和凋亡基因的mRNA水平。免疫组织化学检测发现,STMN1在PCa病例中明显过表达。经Kaplan-Meier生存分析,STMN1过表达与高阶Gleason评分显著相关,且与PCa患者预后较差相关(p < 0.05)。siRNA应用后STMN1基因显著沉默(87.5%)。尤其是侵袭基因如claudin 7、成纤维细胞生长因子8、缺氧诱导因子1亚单位α、肝细胞生长因子、基质金属肽酶2,7等基因在sirna介导的stmn1沉默后显著降低。western blot检测STMN1沉默显著增加caspase 3蛋白表达(p < 0.001)。虽然STMN1沉默对PCa细胞中凋亡和自噬相关基因的诱导没有显著影响,但研究表明,STMN1沉默通过caps3蛋白影响凋亡机制。sirna介导的STMN1沉默可降低PCa细胞系的增殖。人们认为STMN1可以作为晚期前列腺癌的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

siRNA-mediated stathmin1 silencing inhibits proliferation of prostate carcinoma cell line.

siRNA-mediated stathmin1 silencing inhibits proliferation of prostate carcinoma cell line.

siRNA-mediated stathmin1 silencing inhibits proliferation of prostate carcinoma cell line.

siRNA-mediated stathmin1 silencing inhibits proliferation of prostate carcinoma cell line.

Stathmin1 (STMN1) has been proposed as a possible prognostic marker and a potential therapeutic target for some cancers. We aimed to analyze the changes in autophagy, invasion, apoptosis-related genes in prostate cancer (PCa) cell line (PC-3), after small interfering RNA (siRNA)-mediated STMN1 silencing, and also the relationships of STMN1 expression, clinicopathological parameters, and survival (OS) in PCa cases. The STMN1 expressions were analyzed, immunohistochemically, in formalin-fixed paraffin-embedded 75 PCa and 15 benign prostatic hypertrophy (BPH) tissues. The correlation between the levels of expression STMN1, clinicopathological features, and OS was determined in PCa cases. The siRNA-mediated STMN1 incubated PC-3 cells were transfected and compared to negative control siRNAs. We determined mRNA levels in autophagy, invasion, and apoptosis genes with the combination of reverse transcription-polymerase chain reaction (RT-PCR) and western blotting in PC3 cell lines after STMN1 silencing. It was determined that STMN1 was overexpressed significantly in PCa cases, immunohistochemically. The overexpression of STMN1 was significantly correlated with the high-grade Gleason score, and it was associated with a worse prognosis of PCa cases according to the Kaplan-Meier survival analysis (p < 0.05). Significant silencing in STMN1 was determined (87.5%) after siRNA applications. Especially, invasion genes such as claudin 7, fibroblast growth factor 8, hypoxia-inducible factor 1 subunit alpha, hepatocyte growth factor, matrix metallopeptidase 2, 7 genes, markedly, decreased by siRNA-mediated STMN1silencing. STMN1 silencing was determined to significantly increase caspase 3 protein expression by using western blot analysis (p < 0.001). Although STMN1 silencing did not have a significant effect on the induction of apoptosis and autophagy-related genes in PCa cells, it was shown to affect apoptotic mechanisms through the caps3 protein. siRNA-mediated STMN1 silencing decreases proliferation in the PCa cell line. It is thought that STMN1 can serve as a potential therapeutic target in the advanced stage-PCa, especially.

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