Student Scientific Society of Civilization Diseases, Medical University of Lodz, 251 Pomorska, 92-213 Lodz, Poland.
Department of Nucleic Acid Biochemistry, Medical University of Lodz, Pomorska 251, 92-213 Lodz, Poland.
Int J Mol Sci. 2023 Jun 16;24(12):10252. doi: 10.3390/ijms241210252.
Despite significant progress in medicine, pancreatic cancer is one of the most tardily diagnosed cancer and is consequently associated with a poor prognosis and a low survival rate. The asymptomatic clinical picture and the lack of relevant diagnostic markers for the early stages of pancreatic cancer are believed to be the major constraints behind an accurate diagnosis of this disease. Furthermore, underlying mechanisms of pancreatic cancer development are still poorly recognized. It is well accepted that diabetes increases the risk of pancreatic cancer development, however the precise mechanisms are weakly investigated. Recent studies are focused on microRNAs as a causative factor of pancreatic cancer. This review aims to provide an overview of the current knowledge of pancreatic cancer and diabetes-associated microRNAs, and their potential in diagnosis and therapy. miR-96, miR-124, miR-21, and miR-10a were identified as promising biomarkers for early pancreatic cancer prediction. miR-26a, miR-101, and miR-200b carry therapeutic potential, as they not only regulate significant biological pathways, including the TGF-β and PI3K/AKT, but their re-expression contributes to the improvement of the prognosis by reducing invasiveness or chemoresistance. In diabetes, there are also changes in the expression of microRNAs, such as in miR-145, miR-29c, and miR-143. These microRNAs are involved, among others, in insulin signaling, including IRS-1 and AKT (miR-145), glucose homeostasis (hsa-miR-21), and glucose reuptake and gluconeogenesis (miR-29c). Although, changes in the expression of the same microRNAs are observed in both pancreatic cancer and diabetes, they exert different molecular effects. For example, miR-181a is upregulated in both pancreatic cancer and diabetes mellitus, but in diabetes it contributes to insulin resistance, whereas in pancreatic cancer it promotes tumor cell migration, respectively. To conclude, dysregulated microRNAs in diabetes affect crucial cellular processes that are involved in pancreatic cancer development and progression.
尽管医学取得了重大进展，但胰腺癌仍是最难诊断的癌症之一，因此预后较差，存活率低。人们认为，胰腺癌的无症状临床表现和缺乏早期诊断标志物是导致该病准确诊断的主要障碍。此外，胰腺癌发生的潜在机制仍未被充分认识。人们普遍认为糖尿病会增加胰腺癌发生的风险，但确切的机制研究甚少。最近的研究集中在 microRNAs 作为胰腺癌的致病因素上。本文旨在综述当前关于胰腺癌和糖尿病相关 microRNAs 的知识，及其在诊断和治疗方面的潜在应用。miR-96、miR-124、miR-21 和 miR-10a 被鉴定为早期胰腺癌预测有前途的生物标志物。miR-26a、miR-101 和 miR-200b 具有治疗潜力，因为它们不仅调节 TGF-β 和 PI3K/AKT 等重要的生物学途径，而且其重新表达有助于通过降低侵袭性或化学抗性来改善预后。在糖尿病中，microRNAs 的表达也发生变化，如 miR-145、miR-29c 和 miR-143。这些 microRNAs 参与胰岛素信号转导，包括 IRS-1 和 AKT（miR-145）、葡萄糖稳态（hsa-miR-21）以及葡萄糖摄取和糖异生（miR-29c）。尽管在胰腺癌和糖尿病中观察到相同 microRNAs 的表达变化，但它们发挥着不同的分子作用。例如，miR-181a 在胰腺癌和糖尿病中均上调，但在糖尿病中它导致胰岛素抵抗，而在胰腺癌中则促进肿瘤细胞迁移。总之，糖尿病中失调的 microRNAs 影响参与胰腺癌发展和进展的关键细胞过程。
