Expression of mir-21 and mir-143 in cervical specimens ranging from histologically normal through to invasive cervical cancer.
Expression of mir-21 and mir-143 in cervical specimens ranging from histologically normal through to invasive cervical cancer.
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DOI：
10.1371/journal.pone.0028423
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Kiviat NB
中科院分区：
文献类型：
--
作者：
Deftereos G;Corrie SR;Feng Q;Morihara J;Stern J;Hawes SE;Kiviat NB
microRNA表达在致癌过程中受到严重破坏，但有限的证据可用于验证人类临床癌症标本中细胞系模型的结果。microRNA-21（mir-21）和microRNA-143（mir-143）先前已被鉴定为在包括宫颈癌在内的一系列癌症中显著失调。我们的目标是研究宫颈样本中几种研究充分的microRNA种类的表达模式，并将结果与细胞系样本进行比较。我们测量了142福尔马林固定，石蜡包埋（FFPE）宫颈活检组织块，从Dantec肿瘤诊所，达喀尔，塞内加尔的表达mir-21和mir-143。使用基于Taqman的实时PCR测定进行MicroRNA表达分析。同时对72例标本进行蛋白免疫组化染色，观察目的蛋白的表达情况。我们发现mir-21的表达随着临床诊断的恶化而增加，但mir-143与组织学无关。这些观察结果与先前涉及宫颈癌细胞系的报道形成鲜明对比，在这些报道中，mir-143一直下调，但mir-21基本上不受影响。我们还首次鉴定了细胞内程序性细胞死亡蛋白4 PDCD 4的表达;与宫颈上皮内瘤样病变（2-3）或原位癌相比，浸润性宫颈癌（ICC）患者中miR-21的已知靶点显著降低（CIN 2 -3/CIS），尽管mir-21和PDCD 4表达之间没有显著相关性，尽管先前的研究将PDCD 4转录物鉴定为已知的mir-21靶。虽然microRNA生物标志物具有许多有希望的特征，但需要对组织学定义的临床标本中的表达水平进行更多研究，以调查基于发现的研究的临床相关性。鉴于我们观察到mir-21表达水平与宫颈癌恶化的组织学诊断之间存在显著相关性，mir-21可能在预测性筛查中具有一定的实用性。
MicroRNA expression is severely disrupted in carcinogenesis, however limited evidence is available validating results from cell-line models in human clinical cancer specimens. MicroRNA-21 (mir-21) and microRNA-143 (mir-143) have previously been identified as significantly deregulated in a range of cancers including cervical cancer. Our goal was to investigate the expression patterns of several well-studied microRNA species in cervical samples and compare the results to cell line samples. We measured the expression of mir-21 and mir-143 in 142 formalin-fixed, paraffin embedded (FFPE) cervical biopsy tissue blocks, collected from Dantec Oncology Clinic, Dakar, Senegal. MicroRNA expression analysis was performed using Taqman-based real-time PCR assays. Protein immunohistochemical staining was also performed to investigate target protein expression on 72 samples. We found that mir-21 expression increased with worsening clinical diagnosis but that mir-143 was not correlated with histology. These observations were in stark contrast to previous reports involving cervical cancer cell lines in which mir-143 was consistently down-regulated but mir-21 largely unaffected. We also identified, for the first time, that cytoplasmic expression of Programmed Cell Death Protein 4 PDCD4; a known target of mir-21) was significantly lower in women with invasive cervical carcinoma (ICC) in comparison to those with cervical intraepithelial neoplasia (2–3) or carcinoma in situ (CIN2-3/CIS), although there was no significant correlation between mir-21 and PDCD4 expression, despite previous studies identifying PDCD4 transcript as a known mir-21 target. Whilst microRNA biomarkers have a number of promising features, more studies on expression levels in histologically defined clinical specimens are required to investigate clinical relevance of discovery-based studies. Mir-21 may be of some utility in predictive screening, given that we observed a significant correlation between mir-21 expression level and worsening histological diagnosis of cervical cancer.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
DOI：
10.1111/j.1440-1746.2008.05666.x
发表时间：
2009-04-01
影响因子：
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作者：
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作者：
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通讯作者：
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DOI：
10.1016/j.bbrc.2009.03.077
发表时间：
2009-06-05
影响因子：
3.1
作者：
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通讯作者：
Huang, Yiran