AKAP8 promotes ovarian cancer progression and antagonizes PARP inhibitor sensitivity through regulating hnRNPUL1 transcription

作者全名：Mobet, Youchaou; Wang, Haocheng; Wei, Qinglv; Liu, Xiaoyi; Yang, Dan; Zhao, Hongyan; Yang, Yu; Ngane, Rosalie Anne Ngono; Souopgui, Jacob; Xu, Jing; Liu, Tao; Yi, Ping

作者地址：[Mobet, Youchaou; Wang, Haocheng; Wei, Qinglv; Liu, Xiaoyi; Yang, Dan; Zhao, Hongyan; Yang, Yu; Xu, Jing; Liu, Tao; Yi, Ping] Chongqing Med Univ, Affiliated Hosp 3, Dept Obstet & Gynecol, Chongqing 401120, Peoples R China; [Mobet, Youchaou; Ngane, Rosalie Anne Ngono] Univ Douala, Fac Sci, Lab Biochem, POB 24157, Douala, Cameroon; [Wei, Qinglv] Chongqing Med Univ, Childrens Hosp, Chongqing Key Lab Child Infect & Immun, Chongqing 400014, Peoples R China; [Souopgui, Jacob] Univ Libre Bruxelles, Mol Parasitol Lab, IBMM, Inst Mol Biol & Med, Gosselies Campus, B-6041 Gosselies, Belgium

通信作者：Liu, T; Yi, P (通讯作者)，Chongqing Med Univ, Affiliated Hosp 3, Dept Obstet & Gynecol, Chongqing 401120, Peoples R China.

来源：ISCIENCE

ESI学科分类：　

WOS号：WOS:001247781900001

JCR分区：Q1

影响因子：4.6

年份：2024

卷号：27

期号：5

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要：Ovarian cancer (OC) is the highest worldwide cancer mortality cause among gynecologic tumors, but its underlying molecular mechanism remains largely unknown. Here, we report that the RNA binding protein A-kinase anchoring protein 8 (AKAP8) is highly expressed in ovarian cancer and predicts poor prognosis for ovarian cancer patients. AKAP8 promotes ovarian cancer progression through regulating cell proliferation and metastasis. Mechanically, AKAP8 is enriched at chromatin and regulates the transcription of the specific hnRNPUL1 isoform. Moreover, AKAP8 phase separation modulates the hnRNPUL1 short isoform transcription. Ectopic expression of the hnRNPUL1 short isoform could partially rescue the growth inhibition effect of AKAP8-knockdown in ovarian cancer cells. In addition, AKAP8 modulates PARP1 expression through hnRNPUL1, and AKAP8 inhibition enhances PAPR inhibitor cytotoxicity in ovarian cancer. Together, our study uncovers the crucial function of AKAP8 condensation -mediated transcription regulation, and targeting AKAP8 could be potential for improvement of ovarian cancer therapy.

基金机构：National Natural Science Foundation of China [32101164, 82072886]; Natural Science Foundation of Chongqing, China [CSTB2022NSCQ-MSX0897]

基金资助正文：We are grateful to the laboratory members for their helpful and inspiring discussions. We thank the Clinical Research Center of the Third Affiliated Hospital of Chongqing Medical University of China for providing us a good lab environment for our experiment. We also appreciate the excellent cooperation of our colleagues in the Obstetrics and Gynecology Department of the Third Affiliated Hospital of Chongqing Medical University of China. We thank the Biochemistry Department of the Faculty of Sciences of the University of Douala -Cameroon for their assistance. We would like to thank the Institute of Biology and Molecular Medicine of the Universite Libre de Bruxelles -Belgium for their guidance. This work was supported by grants from The National Natural Science Foundation of China (No. 32101164 to Y.Y. and No. 82072886 to P.Y.) and the Natural Science Foundation of Chongqing, China (No. CSTB2022NSCQ-MSX0897 to T.L.) .