外泌体非编码RNA在胰腺癌化疗耐药中的潜在作用

Potential roles of exosomal non-coding RNAs in chemoresistance in pancreatic cancer

胰腺癌是世界上最致命的消化道肿瘤之一,主要与其早期诊断困难、早期发生转移以及对化疗反应不敏感有关.晚期胰腺癌患者可通过化疗提高生存率,包括吉西他滨、铂类药物、5-氟尿嘧啶以及PARP抑制剂等靶向治疗药物.然而,原发性耐药或获得性耐药最终导致胰腺癌患者治疗失败和预后不良.胰腺癌耐药的潜在机制复杂且尚未定论.最近的研究表明,外泌体是ncRNA的最佳天然载体,他们可以通过运输ncRNA调节耐药性.越来越多的证据表明,外泌体非编码RNA,包括microRNA(miRNAs)、长非编码RNA(lncRNAs)、环状RNA(circRNAs),在胰腺癌对化疗药物的耐药性中起着重要的调节作用.在这篇综述中,我们系统地强调了外泌体ncRNAs影响胰腺癌化疗耐药中的新角色和调控机制.此外,我们认为外泌体ncRNAs可以被认为是诊断和预后的潜在生物标志物,以及胰腺癌的新的治疗靶点.

Pancreatic cancer(PC)is one of the deadliest digestive system tumors in the world,primarily attributed to difficulty in early diagnosis,early metastasis,and insen-sitivity to chemotherapy.The survival of advanced PC patients can be improved by chemotherapy,including gemcitabine,platinum drugs,and 5-fluorouracil,and targeted therapy such as PARP inhibitors.Nevertheless,primary or acquired drug resistance ultimately leads to treatment failure and poor prognosis in patients with PC.The mechanism underlying drug resistance in PC is complex and has not been fully elucidated.Recent studies have indicated that exsomes are the best natural carrier of non-coding RNAs(ncRNAs).They can regulate drug resistance by transporting ncRNAs.Accumulating evidence has demonstrated that exosomal ncRNAs,including microRNAs(miRNAs),long noncoding RNAs(lncRNAs),and circular RNAs(circRNAs),play an crucial role in regulating resistance to chemotherapy drugs in PC.In this review,we systematically focus on the emerging role and regulatory mechanisms of exosomal ncRNAs in influencing chemotherapy resistance in PC.We believe that exosomal ncRNAs can be considered as potential biomarkers for the diagnosis and prognosis of PC as well as new therapeutic targets.