Circulating microRNAs in patients with non-alcoholic fatty liver disease

Abstract

AIM:To identify novel non-invasive biomarkers for non-alcoholic fatty liver disease (NAFLD). METHODS:Twenty patients with histologically proven NAFLD and 20 controls were included. All NAFLD cases were scored using the NAFLD activity score. The relative expressions of miR-197, miR-146b, miR-10b, miR181d, miR-34a, miR-122, miR-99a and miR-29a were analyzed using real-time polymerase chain reaction. RESULTS:Serum levels of miR-181d, miR-99a, miR-197 and miR-146b were significantly lower in biopsy-proven NAFLD patients than in the healthy controls. Serum levels of miR-197 and miR-10b were inversely correlated with degree of inflammation and miR-181d and miR99a were inversely correlated with serum gamma glutamyl transferase levels in non-alcoholic steatohepatitis patients. CONCLUSION:NAFLD is associated with altered serum miRNA expression pattern. This study provides clues for defining the non-invasive diagnosis of NAFLD.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; MicroRNA; Noninvasive; Serum markers Core tip: Due to the limitations of liver biopsy, the use of non-invasive markers has emerged in recent years. MicroRNAs (miRNAs) are a class of naturally occurring small noncoding RNAs that regulate gene expression. Altered miRNA expression has been reported in animal and human liver samples in non-alcoholic fatty liver disease (NAFLD). There is, however, only limited information on their detection in blood and their correlation with histological disease severity in patients with NAFLD. For this reason, we measured the serum levels of some miRNAs in non-alcoholic steatohepatitis (NASH) patients. Of these microRNAs, miR-181d, miR99a, miR-197 and miR-146b were expressed at lower levels in NASH patients than in controls. Serum levels of miR-197 and miR-10b were inversely correlated with degree of inflammation and miR-181d and miR-99a were inversely correlated with serum gamma glutamyl transferase levels in NASH patients. Circulating microRNAs in patients with non-alcoholic fatty liver disease 613 Celikbilek M, Baskol M, Taheri S, Deniz K, Dogan S, Zararsız G, Gursoy S, Guven K, Ozbakır O, Dundar M, Yucesoy M. Circulating microRNAs in patients with non-alcoholic fatty liver disease. ORIGINAL ARTICLE

miR-197: A novel biomarker for cancers

“…miR-197 was also lower in biopsy-proven nonalcoholic fatty liver (Celikbilek et al, 2014), primary biliary cirrhosis (Ninomiya et al, 2013), multiple sclerosis1 (Margareta Jernås et al, 2013), uterine leiomyoma (Ling et al, 2015a), type 2 diabetes (Zampetaki et al, 2010) and increased in placentas of preeclampsia (Choi et al, 2013), Graves' disease (Qin et al, 2015). Furthermore, miR-197, in hepatitis B virus infected patients, gradually decreased along with the severity of liver disease symptoms.…”

“…Thus, it was of great concern to investigate the roles and potential mechanisms of key miRNAs in tumorigenic driver pathways. Among them, miR-197, transcribed from the genomic region of chromosome 1p13.3, was found to be significantly dysregulated in a wide range of diseases, such as lung cancer (Remon et al, 2015), breast cancer (Shaker et al, 2015), ovarian cancer (Zou et al, 2015), hepatocellular carcinoma (HCC) , colorectal cancer , thyroid cancer (Weber et al, 2006), head and neck carcinoma (Dai et al, 2011), prostate cancer , follicular thyroid carcinoma (FTC) (Weber et al, 2006), non-alcoholic fatty liver disease (Celikbilek et al, 2014), primary biliary cirrhosis (Ninomiya et al, 2013). Furthermore, increasing evidences had confirmed that miR-197 played a vital role in cell proliferation, apoptosis, differentiation, metastasis and drug resistance, as well as other cellular processes through interacting with particular RNA species (Huang et al, 2014) (Table 1).…”

MicroRNA-197 Promotes Metastasis of Hepatocellular Carcinoma by Activating Wnt/β-Catenin Signaling

“…Consistently, miR-197 has been shown to promote pulmonary metastasis for non-small cell lung cancer [37,46]. miR-197 also participates in the development of a number of types of cancer [26][27][28][29][30][31][32][33][34], including HCC [29,30], indicating the role of miR-197 in cancer.miR-197 also participates in liver fibrosis [35,36], in which Wnt/β-catenin signaling also plays a central role [47].…”

Small but mighty: microRNAs as novel signalling molecules in cancer

“…Dysregulation of miRNA secretion is associated with diverse pathological conditions, including diabetes [25] , liver disease [73] , tissue injury [74] , and cancer [11] . Accordingly, changes in extracellular miRNA profiles may reflect molecular alterations in the cells from which they are derived, and therefore provide unique pathological signatures that aid in disease diagnosis and inform therapeutic strategy.…”