Reduced miR-34a Expression in Normal Cervical Tissues and Cervical Lesions With High-Risk Human Papillomavirus Infection
Reduced miR-34a Expression in Normal Cervical Tissues and Cervical Lesions With High-Risk Human Papillomavirus Infection
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DOI：
10.1111/igc.0b013e3181d63170
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发表时间：
2010-05-01
影响因子：
4.8
通讯作者：
Xie, Xing
中科院分区：
文献类型：
--
作者：
Li, Baohua;Hu, Ying;Xie, Xing
简介：miR-34 a表达减少与高危人乳头瘤病毒（HR-HPV）感染和宫颈癌相关。HR-HPV E6诱导的miR-34 a表达降低是否发生在癌前病变中，甚至在形态学改变之前，仍然不确定。本研究旨在探讨pri-miR-34 a在宫颈病变发生发展中的作用及HPV-16 E6诱导pri-miR-34 a表达改变的机制。在不同的宫颈组织中检测pri-miR-34 a的表达水平，包括有（n = 32）或无（n = 32）HR-HPV感染的正常宫颈上皮，宫颈上皮内瘤变（CIN）伴或不伴HR-HPV感染（n = 32）和宫颈癌（n = 32），通过半定量逆转录聚合酶链反应。将HPV-16 E6表达载体和HPV-16 E6小干扰RNA分别转染293 T细胞和SiHa细胞。结果：pri-miR-34 a在CIN和宫颈癌中的表达明显低于正常宫颈上皮，在CIN 2和CIN 3中的表达明显低于CIN I。pri-miR-34 a在正常宫颈上皮和HR-HPV感染的CIN中的表达明显低于未感染者。结论：pri-miR-34 a不仅在宫颈癌组织中表达降低，而且在宫颈癌前病变组织中表达降低。HR-HPV E6在p53依赖性通路中诱导的miR-34 a表达抑制可能是宫颈癌发生的早发型事件。
Introduction: Reduced miR-34a expression is associated with high-risk human papillomavirus (HR-HPV) infection and cervical cancer. Whether the reduction of miR-34a expression induced by HR-HPV E6 occurs in precancerous lesions, even before morphologic change, is still uncertain. Our study aimed to ascertain the possibility of pri-miR-34a involved in the development of cervical lesions and to explore the mechanism of altered pri-miR-34a expression induced by HPV-16 E6.Methods: The levels of pri-miR-34a expression were examined in different cervical tissues, including normal cervical epithelium with (n = 32) or without (n = 32) HR-HPV infection, cervical intraepithelial neoplasia (CIN) with (n = 32) or without (n = 12) HR-HPV infection, and cervical cancer (n = 32), by semiquantitative reverse transcription-polymerase chain reaction. The HPV-16 E6 expression vector and HPV-16 E6 small interfering RNAs were conducted and transfected into 293T cells and SiHa cells, respectively. The expression of pri-miR-34a and p53 protein was simultaneously analyzed by reverse transcription-polymerase chain reaction and Western blot in cells with gene transfection and without.Results: pri-miR-34a expression was significantly reduced in CIN and cervical cancer compared with normal cervical epithelium, as well as in CIN 2 and CIN 3 compared with CIN I. Moreover, the expression of pri-miR-34a was significantly lower in normal cervical epithelium and CIN with HR-HPV infection than in those without. Simultaneous downregulation or up-regulation of pri-miR-34a and p53 expression was observed in E6-transfected 293T cells or E6 small interfering RNAYtransferred SiHa cells compared with controls.Conclusions: Reduced expression of pri-miR-34a occurs not only in cervical cancer but also in precancerous lesion even before morphologic change. The inhibition of miR-34a expression induced by HR-HPV E6 in the p53-dependent pathway is probably an early-onset event in the development of cervical cancer.