MicroRNA-195 vector influence on the development of gradually induced hepatocellular carcinoma in murine model.

Background: Recent studies implicate the role of microRNAs in the pathogenesis of hepatocellular carcinoma (HCC). This study was designed to induce HCC, in an experimental model, with the prospect to study the molecular pathophysiologic changes accompanying the development of HCC and the effect of miRNA-195 vector on the process of hepatocarcinogenesis.Methodology: This study incorporated three groups of male albino mice; one control group and two other groups injected intraperitoneal with diethylnitrosamine (DEN) weekly for 12 weeks for the gradual induction of HCC. The third group was injected intra-hepatic with miR-195 vector 1 month after DEN injection. At the 8th and 12th weeks post-DEN treatment, the tumor-associated biomarkers alpha-fetoprotein (AFP), vascular endothelial growth factor (VEGF), and tumor necrosis factor-alpha (TNF-α) were assessed in the serum of all mice. Hepatic specimens were subjected to ultra-structural pathological examination as well as to caspase-3 and survivin genes expression analysis.Results: All the assessed serological and molecular parameters of HCC development, in the miRNA-195-treated group of mice, showed a significant increase, versus the DEN-treated group, whereas survivin was significantly down-regulated, in the miR-195-treated group (P < 0.001). Additionally, ultra-structural criteria of HCC were depicted, in the 12th week, in DEN-injected group, versus the 8th week, in the miRNA-195-treated group.Conclusions: Intra-hepatic injection of miRNA-195 vector induced apoptotic gene expression and suppressed anti-apoptotic gene but these favorable anti-cancer effects could not counteract the inflammatory, and subsequently, the oncogenic effect probably caused by vector administration. Therefore, further studies are required to investigate the effect of miRNA in combination with anti-inflammatory medications.

MicroRNA-122a as a non-invasive biomarker for HCV genotype 4-related hepatocellular carcinoma in Egyptian patients.

INTRODUCTION: Hepatitis C virus (HCV) infection persists in most infected individuals and can lead to the development of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) have a crucial role in various liver diseases, especially HCC. The expression profiles of circulating microRNAs have been studied aiming at the identification of novel non-invasive biomarkers. This study aims to develop a non-invasive diagnostic tool based on measuring the serum levels of different miRNAs in order to detect HCV-induced HCC at the early stages of the disease. MATERIAL AND METHODS: Five main miRNAs (miRNA-122a, miRNA-125a, miRNA-139, miRNA-145, and miRNA-199a) were selected according to the literature that demonstrated their unique expression pattern during HCC development. Serum samples were collected from 42 cases of chronic hepatitis C (CHC) without cirrhosis, 45 cases of CHC with cirrhosis (LC), 38 cases of HCC with HCV, and 40 healthy individuals serving as a control. The five miRNAs were measured using real-time reverse transcription PCR. The conventional HCC markers α-fetoprotein (AFP) and des-γ-carboxyprothrombin (DCP) were measured with commercial kits. RESULTS: Serum levels of miRNA-122a, miRNA-125a, miRNA-139, miRNA-145, and miRNA-199a were significantly lower (p < 0.01) in HCC than in CHC and LC groups. As a single marker, miRNA-122a had the highest sensitivity for HCC, followed by miRNA-199a, miRNA-145, miRNA-139, and miRNA-125a. CONCLUSIONS: These findings indicate that measurement of serum levels of miRNA-122a, miRNA-125a, miRNA-139, miRNA-145, and miRNA-199a can differentiate HCC from CHC and LC. Our results suggest that serum miR-122 might serve as a novel and potential noninvasive biomarker for HCV-induced HCC.

Expression analysis of liver-specific circulating microRNAs in HCV-induced hepatocellular Carcinoma in Egyptian patients.

OBJECTIVES: Due to the absence of reliable and accurate biomarkers for the early detection of liver malignancy, circulating microRNAs have recently emerged as great candidates for prompt cancer identification. Therefore, the aim of this study was to investigate the potential of liver-specific circulating microRNAs as an accurate non-invasive diagnostic tool for early diagnosis of hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC). METHODOLOGY: A total of 165 patients were enrolled in this study and categorized into four main groups: 42 chronic hepatitis C (CHC) without cirrhosis, 45 CHC with cirrhosis (LC), 38 HCC with HCV patients, and 40 healthy controls. The expression profiles of seven miRNAs (miR-16, miR-34a, miR-125a, miR-139, miR-145, miR-199a, and miR-221) were analyzed using real-time PCR. RESULTS: Serum levels of miRNA-125a, miRNA-139, miRNA-145, and miRNA199a were significantly lower (p < 0.01) in HCC than in both CHC and LC groups. On the other hand, no significant difference was shown in the expression of miR-16, miR-34a, and miR-221 between the CHC, LC, and HCC groups. MiR-16, miR-34a, and miR-221 were significantly elevated in the HCC group compared to the control group. MiR-34a showed the highest specificity and sensitivity. CONCLUSIONS: The results indicated that the measurement of serum levels of miR-125a, miR-139, miR-145, and miR-199a can help to differentiate HCC from CHC and LC. Also, miR-16, miR-34a, and miR-221 serum levels would have a prognostic value. MiR-34a had the highest specificity and sensitivity, indicating that it might serve as a novel and potential non-invasive biomarker for HCV-induced HCC.