Low PDE4A expression promoted the progression of ovarian cancer by inducing Snail nuclear translocation

作者全名：Wang, Jinlong; Gu, Qiuying; Liu, Yuexi; Huang, Xiaolan; Zhang, Jiajing; Liu, Bin; Li, Ruonan; Hua, Linghu

作者地址：[Wang, Jinlong; Gu, Qiuying; Liu, Yuexi; Huang, Xiaolan; Zhang, Jiajing; Li, Ruonan; Hua, Linghu] Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Chongqing 400016, Peoples R China; [Liu, Bin] Chongqing Med Univ, Coll Basic Med, Mol Med Diagnost & Testing Ctr, Dept Pathol,Affiliated Hosp 1, Chongqing 400016, Peoples R China

通信作者：Li, RN; Hua, LH (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Chongqing 400016, Peoples R China.; Hua, LH (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, 1st You Yi Rd, Yuzhong 400016, Chongqing, Peoples R China.

来源：EXPERIMENTAL CELL RESEARCH

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001253653800001

JCR分区：Q2

影响因子：3.3

年份：2024

卷号：439

期号：2

开始页：　

结束页：　

文献类型：Article

关键词：Cyclic nucleotide phosphodiesterase 4A; Ovarian cancer; EMT; Tumor metastasis; Rolipram; Snail

摘要：Widespread metastasis is the primary reason for the high mortality associated with ovarian cancer (OC), and effective targeted therapy for tumor aggressiveness is still insufficient in clinical practice. Therefore, it is urgent to find new targets to improve prognosis of patients. PDE4A is a cyclic nucleotide phosphodiesterase that plays a crucial role in the occurrence and development in various malignancies. Our study firstly reported the function of PDE4A in OC. Expression of PDE4A was validated through bioinformatics analysis, RT-qPCR, Western blot, and immunohistochemistry. Additionally, its impact on cell growth and motility was assessed via in vitro and in vivo experiments. PDE4A was downregulated in OC tissues compared with normal tissues and low PDE4A expression was correlated with poor clinical outcomes in OC patients. The knockdown of PDE4A significantly promoted the proliferation, migration and invasion of OC cells while overexpression of PDE4A resulted in the opposite effect. Furthermore, smaller and fewer tumor metastatic foci were observed in mice bearing PDE4A-overexpressing OVCAR3 cells. Mechanistically, downregulation of PDE4A expression can induce epithelial-mesenchymal transition (EMT) and nuclear translocation of Snail, which suggests that PDE4A plays a pivotal role in suppressing OC progression. Notably, Rolipram, the PDE4 inhibitor, mirrored the effects observed with PDE4A deletion. In summary, the downregulation of PDE4A appears to facilitate OC progression by modulating the Snail/EMT pathway, underscoring the potential of PDE4A as a therapeutic target against ovarian cancer metastasis.

基金机构：National Natural Science Foundation of China (NFSC) [81572562]; Chongqing Science and Technology Foundation [cstc2021jcyj-msxmX0275]; Chongqing Postgraduate Research and Innovation Project [CYB20149]; Science and Technology Committee of Yuzhong District [20190133]; Hospital Cultivation Fund of the First Affiliated Hospital of CQMU [PYJJ-2022-06]

基金资助正文：The authors thank all patients who participated in this study. We thank the Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, for providing the experimental platform. This study was supported by the National Natural Science Foundation of China (NFSC No. 81572562) , the Chongqing Science and Technology Foundation (cstc2021jcyj-msxmX0275) , the Chongqing Postgraduate Research and Innovation Project (CYB20149) , the Science and Technology Committee of Yuzhong District (20190133) and the Hospital Cultivation Fund of the First Affiliated Hospital of CQMU (PYJJ-2022-06) .