microRNAs roles on apoptosis in pancreatic cancer

Pancreatic cancer (PC) is a disease with a prognosis only of 5-6% of patients. Improving diagnosis, and treatment of PC need a better understanding of the molecular mechanisms and the different pathways implicated in the pathogenesis of PC. In PC, the PI3K/AKT pathway is disrupted. This pathway induces apoptosis, so that disruption causes cancer cell survival and disease progression. Several microRNAs are involved in this pathway, some of which are tumor suppressors and some are oncogenes, As discussed below.miR21 and miR221 decrease the expression of PTEN, NOTCH1, and NOTCH2 in PC and have oncogenic functions. They regulate cell growth by negative regulation of PI3K/AKT pathway. miR221 in normal tissue increase P27, P57, and PUMA expression which are tumor suppressors and inhibit cell proliferation. The expression of miR34 is suppressed in PC and decreases the expression of AKT and Bcl2.miR217 naturally reduces K-RAS expression and inhibits AKT expression, which inhibits cell survival. actually, K-RAS mutations are found in 90% of PC patients in metastatic stage, which results in cell viability and anti-apoptotic activity. Besides, miR217 expression is reduced in PC and as a result, cell growth is going out of control.Another miRNA-mediated therapy is miRNA antagonists. Single-stranded antisense designed for a particular miRNA and binds to it with high stability. These antagonists inhibit the activity of miRs or interferes with miR biogenesis.The assessment of miRNAs involved in PI3K/AKT pathway is imperative as diagnostic biomarkers and therapeutic targets in patients with PC. However, so far, only a few miRNAs have been studied at the functional or molecular levels in PC patients. Further investigations should be performed to identify, characterize and clarify the significant functions of miRNAs involved in PI3K/AKT pathway in the pathology of PC at a molecular level and use them as clinical biomarkers and therapeutic targets.

کلیدواژه ها:

pancreatic cancer ، microRNAs ، PI3K/AKT pathway ، therapeutic targets