Role of let7-g and miR-221 level as potential predictors for overall survival of hepatocellular carcinoma patients

Abstract

Background and study aims: Hepatocellular carcinoma (HCC) is one of the most common cancer types worldwide. A hallmark of epithelial-mesenchymal transition is the loss of epithelial E-cadherin, which is considered an epithelial differentiation marker. MicroRNAs serve vital roles in various biological processes in the cell via post-transcriptional gene regulation. Therefore, the present study aimed to investigate the involvement of certain miRNAs in the progression of HCC.

Patients and methods: A reverse transcription-quantitative PCR assay was conducted to detect the expression levels of 20 EMT-related miRNAs in 36 fresh tissue biopsies from patients with primary HCC compared with healthy controls. Gene expression levels, as well as immunohistochemistry assays, were performed for E-cadherin, ZEB1 and ZEB2 proteins. The correlation between their expression levels and different clinicopathological factors was also assessed.

Results: A significant decrease of E-Cadherin and an increase in ZEB1 expression levels were identified in HCC groups compared with controls, while no significant changes for ZEB2 were found. The absence of E-cadherin membranous protein was observed in ∼48% of the cases examined. Moreover, ZEB1 protein was absent in 46% of E-cadherin positive cases. Upregulation of miR-182, miR-221 and miR-222 expression levels, and downregulation of let-7g, miR-9, miR-16, miR29c, miR122, miR-145, miR-148a, miR-193b, miR-194 and miR-215 expression levels were identified. A positive correlation between let7-g with E-Cadherin expression was reported. No significant association was identified between each of E-cadherin, ZEB1, ZEB2 or miRNAs examined with different clinicopathological features of the patients. Furthermore, the low expression of let7-g and high expression of miR-221 were associated with poorer survival.

Conclusion: Collectively, the present data suggested that let7-g functions as a tumor suppressor in the development of HCC via regulating E-Cadherin. Furthermore, both let7-g and miR-221 may be potential biomarkers for the outcomes of HCC patients.

Keywords: E-cadherin; Hepatocellular carcinoma; Let7-g; MicroRNAs; miR-221.