Ebrahimi Safieh, Hosseini Mina, Ghasemi Faezeh, Shahidsales Soodabeh, Maftouh Mina, Akbarzade Hamed, Parizadeh Seyed Ali Reza, Hassanian Seyed Mahdi, Avan Amir
Department of Medical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Molecular Medicine Group, Department of Modern Sciences and Technologies; Cancer Research Center; School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Curr Pharm Des. 2016;22(42):6444-6450. doi: 10.2174/1381612822666160817095047.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a very poor prognosis, and excessive resistance to chemotherapy. MicroRNAs have been shown to play important roles in PDAC oncogenesis as they can act as both oncogenes and tumor suppressor molecules. Altered expression of specific microRNAs in PDAC has diagnostic and prognostic implications. There is growing body of evidence showing the important role of miR-486-5p and miR-938 for discrimination of PDAC patients from healthy subjects and those with chronic pancreatitis. Additionally the diagnostic features of miR-486-5p were comparable with CA 19-9 for the detection of PDAC patients, suggesting its diagnostic value as a blood-based miRNA in PDAC, although further investigations are warranted for validation of this marker. In addition to these applications, several studies have suggested therapeutic potential of some miRNAs in PDAC. In particular, modulations of let-7, miR-29a, miR-17-5p, miR-365, miR-181b, miR-21, miR-221 and miR-96 are reported to be associated with tumor response. Moreover, enforced expression of miR-17-92 inhibits tumourigenicity and increased chemoresistance in PDAC cancer stem cells via TGF-β1 pathway, while overexpression of miR-96 suppresses cell proliferation, migration, and invasion in a manner associated with KRAS downregulation. In this review we attempt to give an overview about recent preclinical and clinical studies that have addressed the potential use of circulating microRNAs as diagnostic and prognostic biomarkers, their use as therapeutic targets and finally, we discuss the possible role of microRNAs in PDAC chemoresistance.
胰腺导管腺癌（PDAC）是一种侵袭性恶性肿瘤，预后很差，且对化疗具有极强的耐药性。微小RNA已被证明在PDAC的肿瘤发生过程中发挥重要作用，因为它们既可以作为癌基因，也可以作为肿瘤抑制分子。PDAC中特定微小RNA的表达改变具有诊断和预后意义。越来越多的证据表明，miR-486-5p和miR-938在区分PDAC患者与健康受试者以及慢性胰腺炎患者方面具有重要作用。此外，miR-486-5p的诊断特征与CA 19-9在检测PDAC患者方面相当，这表明其作为基于血液的微小RNA在PDAC中的诊断价值，尽管需要进一步研究来验证该标志物。除了这些应用外，一些研究还表明某些微小RNA在PDAC中具有治疗潜力。特别是，据报道let-7、miR-29a、miR-17-5p、miR-365、miR-181b、miR-21、miR-221和miR-96的调节与肿瘤反应有关。此外，miR-17-92的过表达通过TGF-β1途径抑制PDAC癌干细胞的致瘤性并增加化疗耐药性，而miR-96的过表达以与KRAS下调相关的方式抑制细胞增殖、迁移和侵袭。在本综述中，我们试图概述最近的临床前和临床研究，这些研究探讨了循环微小RNA作为诊断和预后生物标志物的潜在用途、它们作为治疗靶点的用途，最后，我们讨论了微小RNA在PDAC化疗耐药性中的可能作用。
