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Cell Signal. 2017 Jul;35:197-207. doi: 10.1016/j.cellsig.2017.04.009. Epub 2017 Apr 14.

Cytidine monophosphate kinase is inhibited by the TGF-β signalling pathway through the upregulation of miR-130b-3p in human epithelial ovarian cancer.

Author information

1
Center Laboratory, Jinshan Hospital, Fudan University, Shanghai 201508, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
2
Center Laboratory, Jinshan Hospital, Fudan University, Shanghai 201508, China.
3
Center Laboratory, Jinshan Hospital, Fudan University, Shanghai 201508, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: guoxiong.xu@fudan.edu.cn.

Abstract

Cytidine monophosphate kinase (CMPK), a member of the nucleoside monophosphate kinase family, plays an important role in the biosynthesis of nucleoside metabolism, DNA repair and tumour development. In this study, we demonstrated for the first time that CMPK was overexpressed in human ovarian epithelial borderline and malignant tumours using tissue microarray. Knockdown of CMPK significantly inhibited epithelial ovarian cancer (EOC) cell proliferation, migration and invasion. Furthermore, CMPK-shRNA inhibited PCNA, MMP-2, MMP-9 and vimentin expression, increased E-cadherin expression and arrested cell cycle at the G2/M phase. Suppression of CMPK resulted in a decrease of EOC cell microtissue formation and colony formation in vitro. Overexpression of miR-130b-3p decreased CMPK expression, whereas anti-miR-130b-3p increased CMPK expression. Moreover, TGF-β1 inhibited the expression of CMPK, which was blocked in the presence of a TGF-β type I receptor, SB431542, and was abolished by the inhibitor of miR-130b-3p, indicating that CMPK is regulated by the TGF-β signalling pathway through the upregulation of miR-130b-3p. Thus, our data identify that overexpression of CMPK occurs in EOC and reveal a mechanism underlying the regulation of CMPK by the TGF-β signalling pathway. We could consider CMPK as an EOC biomarker and targeting CMPK by decreasing its expression may be beneficial in patients with EOC.

KEYWORDS:

TGF-β signalling; Therapeutic target; Tissue microarray; Tumorigenesis; UMP/CMP kinase; miRNA

PMID:
28414100
DOI:
10.1016/j.cellsig.2017.04.009
[Indexed for MEDLINE]

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