Dysregulation of miRNAs Targeting the IGF-1R Pathway in Pancreatic Ductal Adenocarcinoma.

Maria Dobre,Mircea Diculescu,Vlad Herlea,Vasile Daniel Balaban,Elena Milanesi,Mihai Ciocîrlan,Gabriel Constantinescu,Cătălina Vlăduţ

doi:10.3390/cells10081856

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC), the most prevalent neoplastic lethal pancreatic disease, has a poor prognosis and an increasing incidence. The insulin-like growth factor-1 receptor (IGF-1R) signaling pathway is considered to be a contributing factor to the progression, metastasis, and therapy resistance of PDAC. Currently available treatment options for PDAC are limited, but microRNAs (miRNAs) may represent a new therapeutic strategy for targeting genes involved in the IGF-1R signaling pathway. Method: We investigated the expression levels of 21 miRNAs involved in the IGF-1R signaling pathway in pancreatic tissue from 38 patients with PDAC and 11 controls (five patients with chronic pancreatitis and six patients with normal pancreatic tissue). Results: We found 19 differentially expressed miRNAs between the PDAC cases and the controls. In particular, miR-100-5p, miR-145-5p, miR-29c-3p, miR-9-5p, and miR-195-5p were exclusively downregulated in PDAC tissue but not in chronic pancreatitis or normal pancreatic tissues; both control types presented similar levels. We also identified miR-29a-3p, miR-29b-3p, and miR-7-5p as downregulated miRNAs in PDAC tissues as compared with normal tissues but not with pancreatitis tissues. Conclusions: We identified a panel of miRNAs that could represent putative therapeutic targets for the development of new miRNA-based therapies for PDAC.

Highlights

Pancreatic cancer occurs primarily as pancreatic ductal adenocarcinoma (PDAC) and represents the seventh most frequent cause of death by cancer in industrialized countries [1]
We evaluated tumor tissues from patients with Pancreatic ductal adenocarcinoma (PDAC) for the expression of a panel of 21 miRNAs that target genes involved in the insulin-like growth factor-1 receptor (IGF-1R) signaling pathway, and we compared the expression of these miRNAs in noncancerous tissues from patients with chronic pancreatitis or normal pancreatic tissues
Previous studies have identified an association between the progression of PDAC and the overexpression of several growth factor receptors, such as HER [21], EGFR [22], and IGF-1R [23,24,25]

Summary

Introduction

Pancreatic cancer occurs primarily as pancreatic ductal adenocarcinoma (PDAC) and represents the seventh most frequent cause of death by cancer in industrialized countries [1]. As the most common pancreatic cancer, PDAC accounts for about 85% of all cases and has a very poor prognosis, with a five-year survival rate of less than 5% [2]. The insulin and insulin-like growth factor-1 receptor (IGF-1R) signaling pathways are known to enhance the development and progression of PDAC by promoting tumor growth and metastasis and by driving therapy resistance [6]. Available treatment options for PDAC are limited, but microRNAs (miRNAs) may represent a new therapeutic strategy for targeting genes involved in the IGF-1R signaling pathway. Method: We investigated the expression levels of 21 miRNAs involved in the IGF-1R signaling pathway in pancreatic tissue from 38 patients with PDAC and 11 controls (five patients with chronic pancreatitis and six patients with normal pancreatic tissue).

Methods

Results

Conclusion