Kim, Jihye Cho, Young-Jae Ryu, Ji-Yoon Hwang, Ilseon Han, Hee Dong Ahn, Hyung Jun Kim, Woo Young Cho, Hanbyoul Chung, Joon-Yong Hewitt, Stephen M. Kim, Jae-Hoon Kim, Byoung-Gie Bae, Duk-Soo Choi, Chel Hun Lee, Jeong-Won 2024-01-19T18:31:48Z 2024-01-19T18:31:48Z 2021-09-05 2020-01 0090-8258 https://pubs.kist.re.kr/handle/201004/119155 Objective: Cyclin-dependent kinase 7 (CDK7) engages tumor growth by acting as a direct link between the regulation of transcription and the cell cycle. Here, we investigated the clinical significance of CDK7 expression and its potential as a therapeutic target in epithelial ovarian cancer (EOC). Methods: CDK7 expression was examined in 436 ovarian tissues including normal to metastatic ovarian tumors using immunohistochemistry, and its clinical implications were analyzed. Furthermore, we performed in vitro and in vivo experiments using CDK7 siRNA or a covalent CDK7 inhibitor (THZ1) to elucidate the effect of CDK7 inhibition on tumorigenesis in EOC cells. Results: The patient incidence of high CDK7 expression (CDK7(High)) gradually increased from normal ovarian epithelium to EOC (P < 0.001). Moreover, CDK7(High) was associated with an advanced stage and high-grade histology (P = 0.035 and P = 0.011, respectively) in EOC patients and had an independent prognostic significance in EOC recurrence (P = 0.034). CDK7 inhibition with siRNA or THZ1 decreased cell proliferation and migration, and increased apoptosis in EOC cells, and this anti-cancer mechanism is caused by GO/G1 cell cycle arrest. In in vivo therapeutic experiments using cell-line xenograft and PDX models, CDK7 inhibition significantly decreased the tumor weight, which was mediated by cell proliferation and apoptosis. Conclusion: Mechanistic interrogation of CDK7 revealed that it is significantly associated with an aggressive phenotype of EOC, and it has independent prognostic power for EOC recurrence. Furthermore, CDK7 may be a potential therapeutic target for patients with EOC, whether platinum sensitive or resistant. (C) 2019 Elsevier Inc. All rights reserved. English ACADEMIC PRESS INC ELSEVIER SCIENCE NUCLEOTIDE EXCISION-REPAIR CELL-CYCLE TRANSCRIPTIONAL ADDICTION CISPLATIN SENSITIVITY MOLECULAR-MECHANISM IN-VITRO INHIBITION STATISTICS ROLES CDK7 is a reliable prognostic factor and novel therapeutic target in epithelial ovarian cancer Article 10.1016/j.ygyno.2019.11.004 1 GYNECOLOGIC ONCOLOGY, v.156, no.1, pp.211 - 221 GYNECOLOGIC ONCOLOGY 156 1 211 221 scie scopus 000511495700029 2-s2.0-85075857589 Oncology Obstetrics & Gynecology Oncology Obstetrics & Gynecology Article NUCLEOTIDE EXCISION-REPAIR CELL-CYCLE TRANSCRIPTIONAL ADDICTION CISPLATIN SENSITIVITY MOLECULAR-MECHANISM IN-VITRO INHIBITION STATISTICS ROLES Cyclin-dependent kinase 7 Epithelial ovarian cancer Prognosis THZ1 Therapeutic target