Evaluation of the role of miRNA in the regulation of DUSP16 gene and JNK family in Hepatocellular Carcinoma in Egyptian patients

Abstract

Hepatocellular carcinoma (HCC) is considered one of the most public and lethal tumor worldwide. HCC is considered the fifth most common solid tumor in the world and the fourth significant cause of cancer-related death. About eighty percent of new cases is found in developing countries as Egypt, but the incidence is increasing in economically advanced regions, like Japan, Western Europe, and the United States. It has shown that expression level of the different microRNAs correlated with liver cellular processes such as inflammation, hepatocyte regeneration, and apoptosis which indicate their important role in many liver diseases including hepatocellular carcinoma. The main objective of the present study is to correlate between the expression levels of liver-specific miRNAs with the different mitogen-activated protein kinase (MAPK) pathways in primary HCC patients. The expression level of miRNA targeting MAPK pathway, Dual-Specificity Phosphatase 16 (DUSP16), c-Jun N-terminal kinases (JNK) family (JNK1, JNK2, and JNK3) detected in tissue biopsy of 38 primary HCC patients as well as six healthy controls using the (quantitative real time PCR) qRT-PCR technique. Detection of the protein levels for DUSP16, JNK1, and JNK2 was done using immunohistochemistry (IHC) assay. The significant correlation was observed between 10 miRNAs with mRNA of DUSP16, JNK1, JNK2, and JNK3 (miR-18b; miR-30c; miR-30e; miR-99a; miR-126; miR-194; miR-198; miR-215; miR-455 and miR-455-3p). Highly significant downregulation was detected in JNK2 and JNK3 gene expression in HCC patients as compared to controls with P value = 0.016, 0.000, respectively. By Using IHC assay, DUSP16 were detected in 34%, JNK-1 in 82% and JNK-2 in 71% p value < 0.001 compared to control samples that did not show any protein expression of the genes analyzed.