Prognostic significance of low DICER expression regulated by miR-130a in cervical cancer.
Prognostic significance of low DICER expression regulated by miR-130a in cervical cancer.
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miR-130a调控的DICER低表达在宫颈癌中的预后意义
DOI：
10.1038/cddis.2014.127
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发表时间：
2014-05-01
影响因子：
9
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中科院分区：
文献类型：
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Dicer对于microRNA（miRNAs）的成熟至关重要，其失调可能有助于肿瘤的发生和发展。该研究探讨了Dicer及其microRNA转录后调控在宫颈癌中的临床意义。qRT-PCR和免疫组织化学研究了宫颈癌组织中Dicer mRNA和蛋白水平。分析Dicer表达与生存期的关系。miRNA靶标预测鉴定了可能靶向Dicer的miRNA。进行荧光素酶报告基因和功能获得或丧失测定。结果显示，36.7%的宫颈癌组织中Dicer mRNA呈低表达，63.3%的宫颈癌组织中Dicer mRNA呈高表达。在蛋白质水平，51%的病例呈阴性表达，49%的病例呈阳性表达。Dicer mRNA和蛋白表达与宫颈癌远处转移和复发显著相关（分别为P= 0.002和P= 0.012）。多因素考克斯分析显示Dicer低表达（P= 0.016）和肿瘤分期（P= 0.047）是独立的预测因子。在预测靶向Dicer的miRNAs中，RT-PCR检测到10个miRNAs，其表达在Dicer低表达的宫颈癌中显著高于Dicer高表达的宫颈癌，且与Dicer表达水平呈负相关（P<0. 05）。体外实验表明，miR-130 a直接靶向Dicer mRNA，以增强SiHa细胞中的迁移和侵袭。最后，生存分析表明，miR-130 a的高表达与无病生存率低显著相关。综上所述，miR-130 a调控的Dicer表达是宫颈癌重要的潜在预后因素。
Dicer is crucial for the maturation of microRNAs (miRNAs) and its dysregulation may contribute to tumor initiation and progression. The study explored the clinical implications of Dicer and its post-transcriptional regulation by microRNAs in cervical cancer. qRT-PCR and immunohistochemistry investigated Dicer mRNA and protein levels in cervical cancer tissues. The relationship between Dicer expression and survival was analyzed. MiRNA target prediction identified miRNAs that might target Dicer. Luciferase reporter and gain-or loss-of-function assays were performed. The results showed that 36.7% of cervical cancer cases showed low expression of Dicer mRNA and 63.3% cases showed high expression. At the protein level, 51% cases showed negative expression and 49% cases showed positive expression. Dicer mRNA and protein expressions were significantly associated with distant metastasis and recurrence in cervical cancer (P= 0.002 and P= 0.012, respectively). Multivariate Cox analysis indicated that low Dicer expression (P= 0.016) and tumor stage (P= 0.047) were independent predictors. Among the miRNAs predicted to target Dicer, 10 were detected by RT-PCR; their expressions were significantly higher in cervical cancers with lower Dicer expression than in those with higher Dicer expression and were negatively correlated with Dicer expression level (P< 0.05). In vitro experiments demonstrated that miR-130a directly targeted Dicer mRNA to enhance migration and invasion in SiHa cells. Finally, survival analysis indicated that higher expression of miR-130a was significantly associated with poor disease-free survival. Taken together, Dicer expression regulated by miR-130a is an important potential prognostic factor in cervical cancer.