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Progressive miRNA expression profiles in cervical carcinogenesis and identification of HPV‐related target genes for miR‐29
Author(s) -
Li Yang,
Wang Fenfen,
Xu Junfen,
Ye Feng,
Shen Yuanming,
Zhou Jiansong,
Lu Weiguo,
Wan Xiaoyun,
Ma Ding,
Xie Xing
Publication year - 2011
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2873
Subject(s) - carcinogenesis , microrna , cyclin dependent kinase 6 , biology , cancer research , cervical cancer , gene , hpv infection , cancer , malignant transformation , gene expression , cell cycle , genetics , cyclin d1
miRNAs have the potential to act on diverse downstream genes, and miRNA signatures of HPV‐infected tissues may provide insight into HPV‐related carcinogenesis. We set out to profile miRNA expression in HPV‐infected samples and relate this to histological and grade‐specific alterations in the spectrum of cervical carcinogenesis in vivo . A total of 31 miRNAs showed significant and continuous expression along with the progression from normal cervical tissue to cancer, and six of them were validated in 133 samples. By bioinformatics analyses, we established a putative HPV‐associated miRNA–mRNA regulatory network, showing that miR‐29 is the most highly enriched. We also found that YY1 and CDK6 were both positively correlated with E6/E7 RNA expression and targeted by tumour‐suppressive miR‐29. Evidence of miR‐29 involvement in HPV infection was further verified in patient samples and by various experimental approaches. Taken together, our results suggest that HPVs have oncogenic properties at least in part by reshaping the milieu of cellular miRNAs. miR‐29 restrains cell cycle progression and induces apoptosis via YY1 and CDK6 promoting malignant transformation induced by HPV, although the abnormality of miR‐29 in HPV‐infected cells might be regulated in an indirect way. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.