Cyclin‐dependent kinase 9 (CDK9) is a novel prognostic marker and therapeutic target in ovarian cancer. Issue 5 (6th February 2019)

• Record Type: Journal Article
• Authors: Wang, Jinglu; Dean, Dylan C.; Hornicek, Francis J.; Shi, Huirong; Duan, Zhenfeng
• Is Part Of: FASEB journal. Volume 33:Issue 5(2019)
• Page Start: 5990
• Page End: 6000
• Publication Date: 2019-02-06
• Subjects: LDC000067 -- transcription -- apoptosis; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201801789RR
• Languages: English
• ISSNs: 0892-6638

Abstract

ABSTRACT: Despite surgical and chemotherapeutic advances over the past few decades, the prognosis for ovarian cancer remains very poor. Although cyclin‐dependent kinase (CDK) 9 has an established pathogenic role in various cancers, its function in ovarian cancer remains poorly defined. The purpose of this study was to evaluate the expression of CDK9 and its therapeutic potential in ovarian cancer. CDK9 expression was determined by immunohistochemistry in a unique ovarian cancer tissue microarray constructed with paired primary, metastatic, and recurrent tumor tissues from 26 ovarian cancer patients. CDK9 was highly expressed in human ovarian cancer cell lines and was also elevated in metastatic and recurrent ovarian tumor tissue compared with patient‐matched primary ovarian tumor tissue. In addition, increased CDK9 significantly correlated with poor patient prognosis. Inhibition of CDK9 by small interfering RNA or CDK9 inhibitor functionally suppressed RNA transcription elongation, induced apoptosis, and reduced proliferation of ovarian cancer cells. Inhibition of CDK9 also suppressed ovarian cancer cell spheroid growth, clonogenicity formation, and migration activity. Our results reveal CDK9 as a novel prognostic biomarker and a promising therapeutic target for preventing metastasis and recurrence while also improving the overall clinical outcome for ovarian cancer patients.— Wang, J., Dean, D. C., Hornicek, F. J., Shi, H., Duan, Z. Cyclin‐dependent kinase 9 (CDK9) is a novel prognostic marker and therapeutic target in ovarian cancer. FASEB J. 33, 5990–6000 (2019). www.fasebj.org