Abstract

In recent years, a growing body of evidence has provided support for the important role of microRNAs (miRNAs) in the progression of human cancers. A recent study showed that a novel miRNA miR-3650 expression was significantly decreased in hepatocellular carcinoma (HCC). However, the precise role of miR-3650 in HCC have remained poorly understood. In this study, we found that miR-3650 expression was frequently decreased in HCC tissues. Low expression of miR-3650 is positively associated with tumor metastasis and poor survival of HCC patients. Forced expression of miR-3650 significantly inhibited the migration and epithelial-mesenchymal transition (EMT) of HCC cells. Through bioinformatic analysis and luciferase assays, we confirmed that neurofascin (NFASC) is a directly target mRNA of miR-3650. Rescue experiment demonstrated that NAFSC overexpression could partially counteracted the inhibitory effect of miR-3650 in HCC metastasis and EMT. In conclusion, our findings are the first time to demonstrate that reduced expression of miR-3650 in HCC was correlated with tumor metastasis and poor survival. MiR-3650 repressed HCC migration and EMT by directly targeting NFASC. Our findings suggested that miR-3650 may serve as a potential prognostic marker and promising application in HCC therapy.

Highlights

  • Hepatocellular carcinoma (HCC) is the sixth most frequent cancer and the fourth most common cause of cancer-related death worldwide in 2018 [1]

  • The results showed that compared with adjacent normal liver tissues, miR-3650 expression in hepatocellular carcinoma (HCC) tissues was significantly decreased (P < 0.0001, Fig. 1A)

  • MiR-3650 expression was negatively correlated with tumor size, tumor-node metastasis (TNM) stage and Barcelona Clinic Liver Cancer www.aging-us.com (BCLC) stage

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Summary

Introduction

Hepatocellular carcinoma (HCC) is the sixth most frequent cancer and the fourth most common cause of cancer-related death worldwide in 2018 [1]. Great developments in the diagnosis and therapy of this disease in the past decades, the prognosis of HCC patients is still dismal [3, 4]. Most newly diagnosed HCC patients are unresectable distant www.aging-us.com metastasis. The median overall survival (OS) of these patients treated with transcatheter arterial chemoembolization or sorafenib was less than one year because of the high rate of recurrence and metastasis [5, 6]. Many HCC patients with same clinical stage have obviously different outcome, suggesting the inherent heterogeneity of the biological behavior of cancer cells [7]. A better understanding of the underlying mechanisms involved in HCC metastasis will provide potential molecular targets for treatment of HCC metastasis and improve the prognosis of HCC patients

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