Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with increasing incidence and high mortality. Surgical resection is the only potentially curative treatment of patients with PDAC. Because of the late presentation of the disease, about 20 percent of patients are candidates for this treatment. The average survival of resected patients is between 12 and 20 months, with a high probability of relapse. Standard chemo and radiation therapies do not offer significant improvement of the survival of these patients. Furthermore, novel treatment options aimed at targeting oncogenes or growth factors in pancreatic cancer have proved unsuccessful. Thereby, identifying new biomarkers that can detect early stages of this disease is of critical importance. Among these biomarkers, microRNAs (miRNAs) have supplied a profitable recourse and become an attractive focus of research in PDAC. MiRNAs regulate many genes involved in the development of PDAC through mRNA degradation or translation inhibition. The possibility of intervention in the molecular mechanisms of miRNAs regulation could begin a new generation of PDAC therapies. This review summarizes the reports describing miRNAs involvement in cellular processes involving pancreatic carcinogenesis and their utility in diagnosis, survival and therapeutic potential in pancreatic cancer.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with increasing incidence and high mortality
The importance of miRNAs in PDAC has been highlighted by numerous studies that have shown the abnormal expression of different miRNAs can lead to chronic pancreatitis, different grades of pancreatic intraepithelial neoplastic (PanIN) and PDAC [20,21,22,23,24]
Korc and coworkers reported that downregulating Tat-interacting protein 30 (TIP30) and upregulating epidermal growth factor receptor (EGFR) by MicroRNA 10b (miR-10b) microRNA caused epidermal growth factor (EGF)-mediated invasion in pancreatic cancer [37]
Summary
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with increasing incidence and high mortality. The importance of miRNAs in PDAC has been highlighted by numerous studies that have shown the abnormal expression of different miRNAs can lead to chronic pancreatitis, different grades of pancreatic intraepithelial neoplastic (PanIN) and PDAC [20,21,22,23,24] All these studies provide significant insight into altered cellular features such as growth, invasive and metastatic behavior of PDAC cells and have established a close relationship between miRNAs and PDAC progression. Recent data revealed that a comprehensive knowledge of the atypical expression of these miRNAs and reestablishment of their normal expression patterns could produce a favorable therapeutic method and help establish targeted approaches for the preclusion of this disease These aberrantly expressed miRNAs may function either as oncogenic miRNAs (oncomiRs) (Table 1) or tumor suppressor miRNAs (TSmiRs) (Table 2), and they appear to play important roles with respect to the initiation, progression and metastatic growth of distal organs in PDAC. This review summarizes the recent reports describing miRNAs’ involvement in cellular processes involving pancreatic carcinogenesis and their utility in diagnosis, survival prognosis and therapy
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