Ranjha Raju, Aggarwal Surbhi, Bopanna Sawan, Ahuja Vineet, Paul Jaishree
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
PLoS One. 2015 Nov 16;10(11):e0142869. doi: 10.1371/journal.pone.0142869. eCollection 2015.
Ulcerative 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.
Biopsy 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.
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-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.
This 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.
溃疡性结肠炎（UC）是一种炎症性肠病，被认为是对患者健康有巨大影响的重要胃肠道疾病。UC患者结肠的长期炎症会增加患结直肠癌的风险。据报道，微小RNA（miRNA）是炎症与癌症之间的连接纽带。在涉及胃肠道各个区域的克罗恩病（CD）患者中，有miRNA差异表达的报道。本研究旨在剖析印度北部UC患者结肠活检样本中位点特异性的miRNA表达情况。
从UC患者以及直肠乙状结肠区域（RS）和升结肠（AC）的健康对照者中采集活检样本。使用微阵列平台比较RS和AC患者之间的miRNA表达。通过实时荧光定量PCR分析进一步验证差异表达。从医院数据库收集UC相关结直肠癌患者的人口统计学和病理数据，并对癌症位点进行分析评估。
对微阵列平台生成的数据以及定量逆转录-聚合酶链反应（qRT PCR）分析显示，与AC相比，在涉及RS的患者中，六种miRNA，即hsa-miR-146b-5p、hsa-miR-335-3p、hsa-miR-342-3p、hsa-miR-644b-3p、hsa-miR-491-3p、hsa-miR-4732-3p的表达下调。与AC相比，在涉及RS区域的患者中，hsa-miR-141-3p的表达上调。对医院登记的UC患者数据库分析显示，在大多数病例中，结直肠癌的位点主要是结肠的直肠乙状结肠区域。
这是第一项显示UC患者结肠不同位点miRNA差异表达的研究。综合我们的数据和先前的报道，我们提出UC期间miRNA的差异表达可能在直肠乙状结肠区域UC相关结直肠癌的发生中起作用。
