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人乳头瘤病毒改变头颈部鳞状细胞癌细胞系中的 microRNA 谱。

Alteration of microRNA profiles in squamous cell carcinoma of the head and neck cell lines by human papillomavirus.

机构信息

Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

出版信息

Head Neck. 2011 Apr;33(4):504-12. doi: 10.1002/hed.21475.

Abstract

BACKGROUND

Human papillomavirus (HPV)-positive cases of squamous cell carcinoma of the head and neck (SCCHN) have a much better disease outcome compared to SCCHN cases lacking HPV. Differences in microRNA (miRNA) expression may affect their clinical outcomes.

METHODS

The miRNA expression was studied using microarrays and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in HPV-16-positive and HPV-negative SCCHN cell lines. The role of HPV-16 E6 and E7 oncogenes in altering miRNA expression was investigated using human foreskin keratinocytes (HFKs).

RESULTS

The miRNAs miR-363, miR-33, and miR-497 were upregulated, whereas miR-155, miR-181a, miR-181b, miR-29a, miR-218, miR-222, miR-221, and miR-142-5p were downregulated in HPV-positive cells compared to both HPV-negative SCCHN and normal oral keratinocytes. HPV-16 E6 oncogene altered miRNA expression in HFKs and in an HPV-16-positive cell line with E6 knockdown using siRNA.

CONCLUSION

miRNAs differentially expressed in the presence of HPV-16 may provide biomarkers for SCCHN and identify cellular pathways targeted by this virus.

摘要

背景

与 HPV 阴性的头颈部鳞状细胞癌(SCCHN)病例相比,HPV 阳性的 SCCHN 病例的疾病结局要好得多。miRNA 表达的差异可能会影响它们的临床结局。

方法

使用微阵列和定量逆转录-聚合酶链反应(RT-PCR)在 HPV-16 阳性和 HPV 阴性的 SCCHN 细胞系中研究 miRNA 的表达。使用人包皮角质细胞(HFKs)研究 HPV-16 E6 和 E7 癌基因改变 miRNA 表达的作用。

结果

与 HPV 阴性的 SCCHN 和正常口腔角质细胞相比,HPV 阳性细胞中 miR-363、miR-33 和 miR-497 上调,而 miR-155、miR-181a、miR-181b、miR-29a、miR-218、miR-222、miR-221 和 miR-142-5p 下调。HPV-16 E6 癌基因改变了 HFKs 中的 miRNA 表达,以及使用 siRNA 敲低 E6 的 HPV-16 阳性细胞系中的 miRNA 表达。

结论

在 HPV-16 存在的情况下差异表达的 miRNA 可为 SCCHN 提供生物标志物,并鉴定该病毒靶向的细胞途径。

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