High Levels of Prebiotic Resistant Starch in Diet Modulate a Specific Pattern of miRNAs Expression Profile Associated to a Better Overall Survival in Pancreatic Cancer.

Nadia Trivieri,Valerio Pazienza,Riccardo Pracella,Francesco Perri,Tiziana Pia Latiano,Annacandida Villani,Elena Binda,Concetta Panebianco

doi:10.3390/biom11010026

Nadia Trivieri, Valerio Pazienza + Show 6 more

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https://doi.org/10.3390/biom11010026

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Abstract

Dietary patterns are well known risk factors involved in cancer initiation, progression, and in cancer protection. Previous in vitro and in vivo studies underline the link between a diet rich in resistant starch (RS) and slowing of tumor growth and gene expression in pancreatic cancer xenograft mice. The aim of this study was to investigate the impact of a diet rich in resistant starch on miRNAs and miRNAs-target genes expression profile and on biological processes and pathways, that play a critical role in pancreatic tumors of xenografted mice. miRNA expression profiles on tumor tissues displayed 19 miRNAs as dysregulated in mice fed with RS diet as compared to those fed with control diet and differentially expressed miRNA-target genes were predicted by integrating (our data) with a public human pancreatic cancer gene expression dataset (GSE16515). Functional and pathway enrichment analyses unveiled that miRNAs involved in RS diet are critical regulators of genes that control tumor growth and cell migration and metastasis, inflammatory response, and, as expected, synthesis of carbohydrate and glucose metabolism disorder. Mostly, overall survival analysis with clinical data from TCGA (n = 175) displayed that almost four miRNAs (miRNA-375, miRNA-148a-3p, miRNA-125a-5p, and miRNA-200a-3p) upregulated in tumors from mice fed with RS were a predictor of good prognosis for pancreatic cancer patients. These findings contribute to the understanding of the potential mechanisms through which resistant starch may affect cancer progression, suggesting also a possible integrative approach for enhancing the efficacy of existing cancer treatments.

Highlights

Pancreatic cancer (PC) is recognized to be one of the most aggressive and lethal malignancies with a dismal prognosis considering that less than 5% for patients with a surgically resectable disease will survive up to 5 years [1] while for patients with advanced metastasized disease an average survival time of 6 months is expected [2]
Principal component analysis (PCA) displayed that miRNA profiling clustered samples obtained from control versus engineered resistant starch diet (ERSD) fed mice (Figure 1A)
Hierarchical clustering analysis based on the global miRNA expression depicted in Figure 1B clearly distinguished PC mice fed with ERSD to those fed with control nutriment

Summary

Introduction

Pancreatic cancer (PC) is recognized to be one of the most aggressive and lethal malignancies with a dismal prognosis considering that less than 5% for patients with a surgically resectable disease will survive up to 5 years [1] while for patients with advanced metastasized disease an average survival time of 6 months is expected [2]. RS consumption is increasingly deemed to confer health benefits, due to several mechanisms including low glycemic index, improved blood lipid profile, prebiotic function and shaping of gut microbiota, with consequent production of fermentation products, above all short chain fatty acids (SCFAs) [11] By virtue of these effects of RS on gut milieu, most preclinical studies have focused on colorectal cancer (CRC), demonstrating RS ability to increase SCFAs and especially butyrate levels, reduce inflammation and intestinal epithelial cells proliferation [12,13], induce apoptosis of damaged colonic epithelium [14], modulate the cancer-related WNT pathway [15]. The beneficial role of RS in clinical studies on CRC patients, remain controversial

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