El-Moaty Zeinab A, Wasef Maria Wagdy, Elsayed Yara A, Shafiq Amina Sayed, Elnagar Mai A, Mohamed Hadeer Rashad, Elesawyf Ahmed E, Abdel Mageedg Sherif S, Mohammed Osama A, Abdel-Reheim Mustafa Ahmed, Hamad Rabab S, Alshomrani Raydaa Abdullah S, Doghish Ahmed S
Biological Sciences Department, College of Science, King Faisal University, Al-Ahsa, 31982, Saudi Arabia.
Department of Biochemistry, Faculty of Science, Cairo University, Cairo, 12613, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 2. doi: 10.1007/s00210-025-04301-w.
Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), remains one of the deadliest malignancies with a dismal prognosis due to late diagnosis and limited effective treatments. This review explores the multifaceted role of circulating and exosomal microRNAs (miRNAs) in pancreatic cancer progression, metastasis, diagnosis, prognosis, and therapeutic potential. miRNAs-a class of small non-coding RNAs-regulate gene expression post-transcriptionally, influencing key oncogenic and tumor-suppressor pathways. Dysregulated miRNA expression correlates with tumor stages, metastasis, and patient survival, presenting promising biomarkers for early detection and monitoring disease progression. Oncogenic miRNAs like miR-21 and miR-10b are elevated in the serum exosomes of PDAC patients and contribute to tumor growth and therapy resistance by modulating pathways such as Ras/ERK and promoting epithelial-mesenchymal transition. Advances in combining miRNA profiles with traditional markers have significantly improved diagnostic accuracy, highlighting miRNAs as robust tools for early intervention. Furthermore, targeting miRNAs therapeutically, either through anti-miRNA oligonucleotides or modulation of their regulatory networks, offers novel approaches to overcome chemoresistance and impede tumor progression. This review synthesizes current understanding and emerging insights into miRNA-driven molecular mechanisms in pancreatic cancer, underscoring their critical role in shaping future diagnostic and therapeutic landscapes.
胰腺癌，尤其是胰腺导管腺癌（PDAC），仍然是最致命的恶性肿瘤之一，由于诊断较晚且有效治疗手段有限，其预后很差。本综述探讨了循环和外泌体微小RNA（miRNA）在胰腺癌进展、转移、诊断、预后及治疗潜力方面的多方面作用。miRNA是一类小的非编码RNA，可在转录后调节基因表达，影响关键的致癌和肿瘤抑制途径。miRNA表达失调与肿瘤分期、转移及患者生存率相关，为早期检测和监测疾病进展提供了有前景的生物标志物。像miR-21和miR-10b这样的致癌miRNA在PDAC患者的血清外泌体中升高，并通过调节Ras/ERK等途径和促进上皮-间质转化来促进肿瘤生长和治疗抵抗。将miRNA谱与传统标志物相结合的进展显著提高了诊断准确性，突出了miRNA作为早期干预有力工具的地位。此外，通过抗miRNA寡核苷酸或调节其调控网络对miRNA进行治疗靶向，为克服化疗耐药性和阻碍肿瘤进展提供了新方法。本综述综合了目前对胰腺癌中miRNA驱动的分子机制的理解和新见解，强调了它们在塑造未来诊断和治疗格局中的关键作用。
