Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, USA.
FASEB J. 2019 May;33(5):5990-6000. doi: 10.1096/fj.201801789RR. Epub 2019 Feb 6.
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.
尽管过去几十年在手术和化疗方面取得了进展，但卵巢癌的预后仍然非常差。虽然细胞周期蛋白依赖性激酶 (CDK) 9 在各种癌症中具有明确的发病作用，但它在卵巢癌中的作用仍未得到明确界定。本研究旨在评估 CDK9 的表达及其在卵巢癌中的治疗潜力。我们使用 26 名卵巢癌患者的配对原发性、转移性和复发性肿瘤组织构建了独特的卵巢癌组织微阵列，通过免疫组织化学法测定了 CDK9 的表达。CDK9 在人卵巢癌细胞系中高表达，与患者匹配的原发性卵巢肿瘤组织相比，在转移性和复发性卵巢肿瘤组织中也升高。此外，CDK9 的增加与患者预后不良显著相关。用小干扰 RNA 或 CDK9 抑制剂抑制 CDK9 可在功能上抑制 RNA 转录延伸，诱导细胞凋亡，并减少卵巢癌细胞的增殖。抑制 CDK9 还抑制了卵巢癌细胞球体生长、集落形成和迁移活性。我们的研究结果揭示了 CDK9 作为一种新型的预后生物标志物和治疗靶点，可用于预防转移和复发，同时改善卵巢癌患者的整体临床结局。
