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Eur J Cancer. 2011 Sep;47(14):2166-74. doi: 10.1016/j.ejca.2011.04.037. Epub 2011 Jun 1.

Reduced miR-100 expression in cervical cancer and precursors and its carcinogenic effect through targeting PLK1 protein.

Author information

1
Women's Reproductive Health Key Laboratory of Zhejiang Province, Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Abstract

AIM:

Although aberrant miRNAs expression has been documented, altered miR-100 expression in cervical cancer and precursor tissues and its carcinogenic effect and mechanism remain unexplored. The aim of our study was to investigate the role of miR-100 alteration in cervical carcinogenesis.

METHODS:

The expression of miR-100 was examined by quantitative real-time reverse transcriptase PCR (qRT-PCR) in 125 cervical tissues including normal cervical epithelium, cervical intraepithelial neoplasia (CIN), and cervical cancer, as well as in five cervical cell lines. Through modulating miR-100 expression using miR-100 inhibitor or mimic in vitro, cell growth, cycle and apoptosis were tested separately by MTT or flow cytometry and meanwhile Polo-like kinase1 (PLK1) mRNA and protein expressions were detected by qRT-PCR and immunoblotting. The expression of PLK1 in 125 cervical tissues was also examined by immunohistochemical staining and the correlation between miR-100 and PLK1 expression in the same tissues was analysed. Finally, HPV-16 E6/E7 expression was modulated by gene transfection and subsequently the level of miR-100 was examined by qRT-PCR.

RESULTS:

The miR-100 expression showed a significantly and gradually reduced tendency from low-grade CIN, high-grade CIN to cervical cancer tissues and a significant decrease in HPV positive cervical cancer cell lines. The modulation of miR-100 expression remarkably influenced cell proliferation, cycle and apoptosis, as well as the level of PLK1 protein, but not mRNA, in vitro experiments. PLK1 expression was negatively correlated with miR-100 expression in CIN3 and cervical cancer tissues. The modulation of HR-HPV E6/E7 expression did not change miR-100 level.

CONCLUSIONS:

The reduced miR-100 expression participates in the development of cervical cancer at least partly through loss of inhibition to target gene PLK1, which probably occurs in a relative late phase of carcinogenesis. HR-HPV E6/E7 may not directly regulate miR-100 expression in cervical cells.

PMID:
21636267
DOI:
10.1016/j.ejca.2011.04.037
[Indexed for MEDLINE]

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