microRNAs已经被发现是基因表达的重要调控因子,它们改变基因表达的作用与癌症发生及肿瘤增殖密切相关。因此,microRNAs能够成为潜在的癌症标记物及治疗靶点。
虽然已有的证据表明了microRNAs的异常表达与子宫内膜癌有关,但是microRNAs对子宫内膜癌的预后意义有关的数据仍然有限。
近日,美国纽约州立石溪大学的研究人员做了一项关于microRNAs的研究。这项研究的目的在于,通过分析福尔马林固定的石蜡包埋的组织,来研究子宫内膜癌中有关的重要microRNAs的预后作用。
实验中,使用试剂盒提取了来自48对正常的及子宫内膜癌标本的总RNAs。其中,miR-26a、let-7g、miR-21、miR-181b、miR-200c、miR-192、miR-215、miR-200c及miR-205的表达通过实时定量RT-PCR分析。差异表达的miRNAs通过免疫组化被定量,数据分析则通过GraphPad Prism 5.0处理。
结果发现,对比于正常组织,miR-200c(P<0.0001)及miR-205(P<0.0001)的表达水平在子宫内膜瘤中被显著提高。
Kaplan-Meier生存分析显示,高水平的miR-205表达与不良的病人存活率有关(hazard ratio,0.377;Logrank test,P=0.028)。此外,在子宫内膜癌中发现,对比于正常组织,靶向抑癌基因(PTEN)的miR-205的表达下降。
这表明,在子宫内膜癌,miR-205将是一个很有潜能的子宫内膜癌预后标记物。相关论文发表在3月13日的PLoS ONE。(生物谷Deepblue编译)
doi: 10.1371/journal.pone.0035158
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Prognostic Significance of miR-205 in Endometrial Cancer
Mihriban Karaayvaz, Cecilia Zhang, Sharon Liang, Kenneth R. Shroyer, Jingfang Ju.
microRNAs have emerged as key regulators of gene expression, and their altered expression has been associated with tumorigenesis and tumor progression.
Thus, microRNAs have potential as both cancer biomarkers and/or potential novel therapeutic targets.Although accumulating evidence suggests the role of aberrant microRNA expression in endometrial carcinogenesis, there are still limited data available about the prognostic significance of microRNAs in endometrial cancer.The goal of this study is to investigate the prognostic value of selected key microRNAs in endometrial cancer by the analysis of archival formalin-fixed paraffin-embedded tissues.Total RNAs were extracted from 48 paired normal and endometrial tumor specimens using Trizol based approach.The expression of miR-26a, let-7g, miR-21, miR-181b, miR-200c, miR-192, miR-215, miR-200c, and miR-205 were quantified by real time qRT-PCR expression analysis.Targets of the differentially expressed miRNAs were quantified using immunohistochemistry. Statistical analysis was performed by GraphPad Prism 5.0.The expression levels of miR-200c (P<0.0001) and miR-205 (P<0.0001) were significantly increased in endometrial tumors compared to normal tissues.Kaplan-Meier survival analysis revealed that high levels of miR-205 expression were associated with poor patient overall survival (hazard ratio, 0.377; Logrank test, P = 0.028).Furthermore, decreased expression of a miR-205 target PTEN was detected in endometrial cancer tissues compared to normal tissues.miR-205 holds a unique potential as a prognostic biomarker in endometrial cancer.