Pilot study identifying circulating miRNA signature specific to alcoholic chronic pancreatitis and its implication on alcohol-mediated pancreatic tissue injury

Bishnupriya Chhatriya; Piyali Sarkar; Debashis Nath; Sukanta Ray; Kshaunish Das; Saroj K Mohapatra; Srikanta Goswami

doi:10.1002/jgh3.12389

Pilot study identifying circulating miRNA signature specific to alcoholic chronic pancreatitis and its implication on alcohol-mediated pancreatic tissue injury

JGH Open. 2020 Jul 15;4(6):1079-1087. doi: 10.1002/jgh3.12389. eCollection 2020 Dec.

Authors

Bishnupriya Chhatriya¹, Piyali Sarkar², Debashis Nath³, Sukanta Ray⁴, Kshaunish Das⁴, Saroj K Mohapatra¹, Srikanta Goswami¹

Affiliations

¹ National Institute of Biomedical Genomics Kalyani India.
² Department of Cytogenetics Tata Medical Centre Kolkata India.
³ Department of Medicine Indira Gandhi Memorial Hospital Agartala India.
⁴ School of Digestive and Liver Diseases Institute of Post Graduate Medical Education and Research Kolkata India.

Abstract

Background and aim: Alcohol exerts its effects on organs in multiple ways. Alcoholic chronic pancreatitis (ACP) is a disease in which alcohol triggers the pathological changes in pancreas, leading to chronic inflammation and fibrosis. The molecular mechanism behind these changes is not clear. Identification of key circulating miRNA changes in ACP patients and determination of the fraction that is secreted from diseased pancreas not only could serve as potential biomarker for assessing disease severity, but also could help identifying the molecular alterations prevailing in the organ precipitating the disease, to some extent.

Methods: We performed microRNA microarray using the Affymetrix miRNA 4.0 platform to identify differentially expressed miRNAs in serum of ACP patients as compared to alcoholic control individuals and then found out how many of them could be pancreas-specific and exosomally secreted. We further analyzed a pancreatitis-specific gene expression data set to find out the differentially expressed genes in diseased pancreas and explored the possible role of those selected miRNAs in regulation of gene expression in ACP.

Results: We identified 14 miRNAs differentially expressed in both serum and pancreas and also identified their experimentally validated targets. Transcription factors modulating the miRNA expression in an alcohol-dependent manner were also identified and characterized to derive the miRNA-gene-TF interaction network responsible for progression of the disease.

Conclusions: Differentially expressed miRNA signature demonstrated significant changes in both pro- and anti-inflammatory pathways probably balancing the chronic inflammation in the pancreas. Our findings also suggested possible involvement of pancreatic stellate cells in disease progression.

Keywords: alcohol; chronic pancreatitis; microRNA; pancreatic injury.