MicroRNA Levels in Cervical Cancer Samples and Relationship with Lesion Grade and HPV Infection.

Carolina R Hoelzle, Solène Arnoult, Cinthya R M Borém, Mariana Ottone, Kênia C S F de Magalhães, Istéfani L da Silva, Renata T Simões
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引用次数: 6

Abstract

Background: miR-21, miR-214 and miR-let-7a are three validated and well-known miRNAs. miR-21 is described as an "oncomir" while miR-214 and miR-let-7a are described mainly as tumor suppressors. The role of these miRNAs remains unclear in cervical cancer, an important malignancy among women worldwide and responsible for many deaths every year.

Objective: The objective of this study is to describe the expression profile of miR-21, miR-214 and miR-let-7a in plasma and in cervical scraping from a control group and patients with different grades of cervical lesions and invasive cervical cancer and correlate with HPV infection groups.

Methods: Plasma and cervical scraping were submitted to DNA and RNA extraction. HPV detection and typing were performed by conventional PCR followed by PAGE to amplicons interpretation. The miRNA relative expression in plasma and cervical scraping samples was performed by real time PCR using specific TaqMan probes.

Results: miR-21 (p=0.0277) and miR-214 (p=0.0151) were up-regulated in cervical scraping samples of invasive cervical cancer (ICC) group. However, miR-214 was also up-regulated in the LSIL group (p=0.0062). Both miRNAs were not related to HPV infection. However, miR-let-7a was higher in HPV positive plasma samples (p=0.0433) than in HPV negative plasma samples and the correlation analysis confirmed the association between the levels of this miRNA with the presence of HPV (p=0.0407; r=0.3029), but not with lesion grade (p>0.05).

Conclusion: Our results suggest that miR-21 is related to cervical cancer progression and miR-214 appears to have an ambiguous role in cervical lesions. miR-let-7a may be upregulated at a systemic level in patients with HPV infection.

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宫颈癌样本中的MicroRNA水平及其与病变级别和HPV感染的关系。
背景:miR-21、miR-214和miR-let-7a是三种经过验证且众所周知的mirna。miR-21被描述为“肿瘤抑制因子”,而miR-214和miR-let-7a主要被描述为肿瘤抑制因子。这些mirna在宫颈癌中的作用尚不清楚,宫颈癌是全世界妇女的一种重要恶性肿瘤,每年造成许多人死亡。目的:本研究的目的是描述miR-21, miR-214和miR-let-7a在对照组和不同程度宫颈病变和浸润性宫颈癌患者的血浆和宫颈刮痧中的表达谱,并与HPV感染组相关。方法:血浆和宫颈刮痧进行DNA和RNA提取。采用常规PCR进行HPV检测和分型,然后用PAGE对扩增子进行解释。采用特异性TaqMan探针实时荧光定量PCR检测血浆和宫颈刮痧标本中miRNA的相对表达。结果:miR-21 (p=0.0277)和miR-214 (p=0.0151)在侵袭性宫颈癌(ICC)组宫颈刮痧标本中表达上调。然而,miR-214在LSIL组中也上调(p=0.0062)。这两种mirna与HPV感染无关。然而,miR-let-7a在HPV阳性血浆样本中高于HPV阴性血浆样本(p=0.0433),相关性分析证实了该miRNA水平与HPV存在之间的相关性(p=0.0407;R =0.3029),但与病变分级无关(p>0.05)。结论:我们的研究结果表明,miR-21与宫颈癌的进展有关,而miR-214在宫颈病变中的作用似乎不明确。在HPV感染患者中,miR-let-7a可能在全身水平上调。
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