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

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.

• Authors: Daibing Zhou, Lingyun Zhang, Wenwen Sun, Wencai Guan, Qunbo Lin, Weimin Ren, Jihong Zhang, Guoxiong Xu
• Journal: Cellular signalling (Cell Signal) Vol. 35 Pg. 197-207 (07 2017) ISSN: 1873-3913 [Electronic] England
• PMID: 28414100 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide
• Benzamides
• Cadherins
• Dioxoles
• MIRN130 microRNA, human
• MicroRNAs
• Neoplasm Proteins
• Receptors, Transforming Growth Factor beta
• Transforming Growth Factor beta
• cytidylate kinase
• Nucleoside-Phosphate Kinase

Topics

• Adolescent
• Adult
• Aged
• Benzamides (administration & dosage)
• Cadherins
• Carcinoma, Ovarian Epithelial
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Dioxoles (administration & dosage)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Neoplasm Proteins (genetics)
• Neoplasms, Glandular and Epithelial (genetics, pathology)
• Nucleoside-Phosphate Kinase (genetics, metabolism)
• Ovarian Neoplasms (genetics, pathology)
• Receptors, Transforming Growth Factor beta (genetics)
• Signal Transduction
• Tissue Array Analysis
• Transcriptional Activation (genetics)
• Transforming Growth Factor beta (genetics, metabolism)