Site-Specific MicroRNA Expression May Lead to Different Subtypes in Ulcerative Colitis.

Raju Ranjha,Jaishree Paul,Vineet Ahuja,Sawan Bopanna,Surbhi Aggarwal,Ratna B Ray

doi:10.1371/journal.pone.0142869

Raju Ranjha, Jaishree Paul + Show 4 more

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https://doi.org/10.1371/journal.pone.0142869

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Abstract

Background and AimUlcerative Colitis (UC) is a type of inflammatory bowel disease, considered as an important disease of gastrointestinal tract having a huge impact on the health of the patient. Prolonged inflammation of colon in UC patients increases the risk of developing colorectal cancer. MiRNA are reported as a connecting link between inflammation and cancer. Differential miRNA expression is reported in Crohn’s disease (CD) patients involving various regions of the gastrointestinal tract. The current study was performed to dissect out the site specific miRNA expression in the colon biopsy samples of UC patients from Northern India.MethodsBiopsy samples were collected from UC patients and healthy controls from Rectosigmoid Area (RS) and Ascending Colon (AC). MiRNA expression was compared between patients with RS and AC using a microarray platform. Differential expression was further validated by Real Time PCR analysis. Demographic and pathological data of UC -associated CRC patients was collected from the hospital database and analyzed for assessing the site of cancer.ResultsUpon analysis of data generated on a microarray platform and qRT PCR revealed that the expression of six miRNAs hsa-miR-146b-5p, hsa-miR-335-3p, hsa-miR-342-3p, hsa-miR-644b-3p, hsa-miR-491-3p, hsa-miR-4732-3p were downregulated in patients where RS was involved as compared to AC. The expression of hsa-miR-141-3p was upregulated in patients where RS region was involved as compared to AC. Analysis of the registered UC patient’s database from the hospital revealed that the site of CRC was predomimnantly the rectosigmoid region of the colon in most of the cases.ConclusionThis is the first study to show the differential expression of miRNA involving different sites of colon in UC patients. Taking our data and previous reports into consideration, we propose that differential miRNA expression during UC perhaps contribute in the development of UC-associated CRC at the rectosigmoid area.

Highlights

Inflammatory bowel disease (IBD) is a chronic inflammatory disease characterized by severe inflammation of the small bowel and/or the colon leading to recurrent diarrhea and abdominal pain
Upon analysis of data generated on a microarray platform and qRT PCR revealed that the expression of six miRNAs hsa-miR-146b-5p, hsa-miR-335-3p, hsa-miR-342-3p, hsa-miR644b-3p, hsa-miR-491-3p, hsa-miR-4732-3p were downregulated in patients where Rectosigmoid Area (RS) was involved as compared to Ascending Colon (AC)
Analysis of the registered Ulcerative Colitis (UC) patient’s database from the hospital revealed that the site of colorectal cancer (CRC) was predomimnantly the rectosigmoid region of the colon in most of the cases. This is the first study to show the differential expression of miRNA involving different sites of colon in UC patients

Summary

Introduction

Inflammatory bowel disease (IBD) is a chronic inflammatory disease characterized by severe inflammation of the small bowel and/or the colon leading to recurrent diarrhea and abdominal pain. Chronic inflammation has been suggested to increase the risk of developing cancer [2]. Patients with ulcerative colitis and Crohn's disease are at increased risk of developing colorectal cancer (CRC) [3,4,5,6] Site of UC associated colorectal cancer in patients has been identified as the rectosigmoid area in 59% of cases [4]. MiRNA can interact with mRNA by binding to 3`UTR and can regulate gene expression at post transcriptional level. It can regulate gene expression either by translational repression or mRNA degradation [7,8]. Prolonged inflammation of colon in UC patients increases the risk of developing colorectal cancer.

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