我们之前阐明了 CDKN1A 反义 DNA 损伤激活 RNA 的长非编码 RNA 启动子 (PANDAR) 作为 p53 依赖性癌基因，可促进卵巢癌 (OC) 的顺铂耐药。有趣的是，在 p53 突变的顺铂耐药患者中发现了高水平的 p53 独立 PANDAR。在这里，我们的研究探讨了PANDAR在p53突变体OC顺铂耐药中的新作用和潜在机制。A2780和A2780-DDP细胞作为OC顺铂敏感和顺铂耐药细胞。 HO-8910PM 细胞被构建化疗诱导的细胞外囊泡 (Chemo-EV)。采用透射电子显微镜 (TEM) 和纳米颗粒跟踪分析来评估 Chemo-EV。使用细胞计数试剂盒8和集落形成测定评估细胞活力。使用膜联蛋白 V 和碘化丙啶染色评估细胞凋亡。通过 RNA 免疫沉淀和荧光原位杂交验证了 PANDAR、丝氨酸和富含精氨酸的前体 mRNA 剪接因子 9 (SRSF9) 之间的关系。采用肿瘤异种移植实验来评估 PANDAR-Chemo-EVs 对体内 OC 顺铂耐药的影响。对肿瘤组织进行免疫荧光染色和免疫组织化学检测。p53突变的OC患者中PANDAR水平升高。 PANDAR 外排在顺铂条件下通过外泌体产生。此外，OC细胞系的外泌体携带PANDAR，可显着提高体外细胞存活率和化疗耐药性以及体内肿瘤进展和转移。在顺铂诱导的应激过程中，随着 PANDAR 的增加和顺铂反应减弱的细胞凋亡，SRSF9 被招募到核体中。此外，SRSF9 显着增加了 OC 中 SIRT4/SIRT6 mRNA 的比例。顺铂诱导的外泌体转移 PANDAR，并通过顺铂应激暴露后积累 SRSF9 导致 OC 细胞生存的快速适应。© 2023。亚洲妇科肿瘤学会，韩国学会日本妇科肿瘤学会和日本妇科肿瘤学会。

We previously elucidated that long non-coding RNA Promoter of CDKN1A Antisense DNA damage Activated RNA (PANDAR) as a p53-dependent oncogene to promote cisplatin resistance in ovarian cancer (OC). Intriguingly, high level of p53-independent PANDAR was found in cisplatin-resistant patients with p53 mutation. Here, our study probed the new roles and the underlying mechanisms of PANDAR in p53-mutant OC cisplatin-resistance.A2780 and A2780-DDP cells were served as OC cisplatin-sensitive and cisplatin-resistant cells. HO-8910PM cells were subjected to construct chemotherapy-induced extracellular vesicles (Chemo-EVs). Transmission electron microscopy (TEM) and nanoparticle tracking analysis were employed to evaluate Chemo-EVs. Cell viability was assessed using cell counting kit-8 and colony formation assays. Cell apoptosis was assessed using Annexin V and propidium iodide staining. The relationships between PANDAR, serine and arginine-rich pre-mRNA splicing factor 9 (SRSF9) were verified by RNA immunoprecipitation and fluorescence in situ hybridization. Tumor xenograft experiment was employed to evaluate the effects of PANDAR-Chemo-EVs on OC cisplatin-resistance in vivo. Immunofluorescent staining and immunohistochemistry were performed in tumor tissue.PANDAR level increased in OC patients with p53-mutation. PANDAR efflux enacted via exosomes under cisplatin conditions. Additionally, exosomes from OC cell lines carried PANDAR, which significantly increased cell survival and chemoresistance in vitro and tumor progression and metastasis in vivo. During cisplatin-induced stress, SRSF9 was recruited to nuclear bodies by increased PANDAR and muted apoptosis in response to cisplatin. Besides, SRSF9 significantly increased the ratio of SIRT4/SIRT6 mRNA in OC.Cisplatin-induced exosomes transfer PANDAR and lead to a rapid adaptation of OC cell survival through accumulating SRSF9 following cisplatin stress exposure.© 2023. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.