Clinical implications of miRNAs in the pathogenesis, diagnosis and therapy of pancreatic cancer

Abstract

Despite considerable progress being made in understanding pancreatic cancer (PC) pathogenesis, it still remains the 10th most often diagnosed malignancy in the world and 4th leading cause of cancer related deaths in the United States with a five year survival rate of only 6%. The aggressive nature, lack of early diagnostic and prognostic markers, late clinical presentation, and limited efficacy of existing treatment regimens makes PC a lethal cancer with high mortality and poor prognosis. Therefore, novel reliable biomarkers and molecular targets are urgently needed to combat this deadly disease. MicroRNAs (miRNAs) are short (19–24 nucleotides) non-coding RNA molecules implicated in the regulation of gene expression at post-transcriptional level and play significant roles in various physiological and pathological conditions. Aberrant expression of miRNAs has been reported in several cancers including PC and is implicated in PC pathogenesis and progression, suggesting their utility in diagnosis, prognosis and therapy. In this review, we summarize the role of several miRNAs that regulate various oncogenes (KRAS) and tumor suppressor genes (p53, p16, SMAD4 etc) involved in PC development, their prospective roles as diagnostic and prognostic markers and their therapeutic targets.

Plasma microRNA panels to diagnose pancreatic cancer: Results from a multicenter study

“…Sensitive and specific biomarkers to identify patients with pancreatic cancer at an early stage are needed [21–23]. This study describes 2 novel panels of miRNAs for diagnosing pancreatic cancer using the combination of 3 or 6 miRNAs in plasma.…”

MicroRNA-1291 targets the FOXA2-AGR2 pathway to suppress pancreatic cancer cell proliferation and tumorigenesis

“…There are also some studies demonstrating that a number of miRNAs are aberrantly expressed in pancreatic cancer cells/tissues and involved in the regulation of many pancreatic cancer related genes [17–27]. Therefore, investigation of novel miRNA regulatory pathways may offer insights into identification of new pancreatic oncotargets and development of new therapeutics [7, 28, 29]. …”

Circulating microRNAs as diagnostic biomarkers for pancreatic cancer

“…[4] MiRNAs are small (19-24 nucleotides) noncoding RNAs playing an important gene-regulatory role in the post-transcriptional phase. [5] Several studies have identified key miRNAs involved in tumor development and progression [6] Importantly, miRNAs are stable in body fluids, [7] either in secreted microvesicles or bound to carrier proteins. This offers a unique opportunity to exploit miRNAs as potential biomarkers for early detection of various cancers, including PDAC.…”