MicroRNAs in Pancreatic Cancer: Involvement in Carcinogenesis and Potential Use for Diagnosis and Prognosis

Abstract

Pancreatic cancer is one of the most fatal malignancies with increasing incidence and high mortality. Possibilities for early diagnosis are limited and there is currently no efficient therapy. Molecular markers that have been introduced into diagnosis and treatment of other solid tumors remain unreciprocated in this disease. Recent discoveries have shown that certain microRNAs (miRNAs) take part in fundamental molecular processes associated with pancreatic cancer initiation and progression including cell cycle, DNA repair, apoptosis, invasivity, and metastasis. The mechanism involves both positive and negative regulation of expression of protooncogenes and tumor suppressor genes. Various miRNAs are expressed at different levels among normal pancreatic tissue, chronic pancreatitis, and pancreatic cancer and may therefore serve as a tool to differentiate chronic pancreatitis from early stages of cancer. Other miRNAs can indicate the probable course of the disease or determine the survival prognosis. In addition, there is a growing interest directed at the understanding of miRNA-induced molecular mechanisms. The possibility of intervention in the molecular mechanisms of miRNAs regulation could begin a new generation of pancreatic cancer therapies. This review summarizes the recent reports describing functions of miRNAs in cellular processes underlying pancreatic cancerogenesis and their utility in diagnosis, survival prognosis, and therapy.

Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma

“…Many of the miRs that were differentially abundant across the clusters (Figure 5B, Table S6, Figure S4C) have been reported as prognostic, as differentially abundant between non-neoplastic and neoplastic tissue, or as functionally involved in signalling pathways in pancreatic cancer (Frampton et al, 2015; Halkova et al, 2015; Hernandez and Lucas, 2016; Lee et al, 2015; Lou et al, 2013; Sun et al, 2015). For example, miR-21 has been reported to be prognostic in pancreatic cancer (Frampton et al, 2015), and to be more abundant in tumors than in non-neoplastic pancreatic tissue (Halkova et al, 2015; Hernandez and Lucas, 2016). We noted that RNF43 mutations were significantly enriched (p = 3.7·10 −3 , Fisher exact test) in miR cluster 2 (Figure 5A).…”

MicroRNA 141 Expression Is a Potential Prognostic Marker of Biliary Tract Cancers

“…Furthermore, few biomarkers except CA 19-9 are known in biliary tract cancer 2. miRNAs which are small noncoding RNAs have been suggested as biomarkers in gastrointestinal solid malignancies including esophageal cancer, pancreatic cancer, and liver cancer 4–6. In that aspect, miRNAs could be candidate prognostic biomarkers in biliary tract cancer although there are still limited data 10–12.…”

“…It has important functions such as posttranscriptional regulation of gene expression and silencing in normal cells. Compared to normal cells, many miRNAs are involved and recognized as new biomarkers in gastrointestinal solid malignancies such as pancreatic, esophageal, and hepatocellular cancers 4–6. However, there were limited studies about miRNA in biliary tract cancers although there was a report that miRNA 141 was highly overexpressed in malignant cholangiocytes and appeared to be a regulator of tumor cell proliferation in vitro 7…”

Nutrients and the Pancreas: An Epigenetic Perspective

“…Multiple cellar functions were found to be inhibited by let-7 miRNA, including Kras expression [75]. Other miRNAs were found to effect pathways involved in cell cycle and proliferation, DNA repair, apoptosis, invasivity, and metastasis in cancers of the pancreas [17,22,75,79,80]. Several miRNAs have also been implicated in β-cell dysfunction, thereby affecting insulin regulation in association with type 2 diabetes [26,68,76,81] and potentially pancreatic cancer.…”