Abstract

In recent decades, an increasing number of studies have demonstrated that numerous microRNAs (miRNAs) are dysregulated in hepatocellular carcinoma (HCC); these aberrantly expressed miRNAs are contributing regulators of HCC formation and progression. Thus, revealing the biological roles of miRNAs in HCC may provide novel information on the identification of effective therapeutic targets and valuable diagnosis methods. Herein, reverse transcription‑quantitative PCR was performed to determine the expression profile of miRNA‑584 (miR‑584) in HCC tissues and cell lines. Cell Counting Kit‑8 and cell invasion assays were utilized to evaluate the influence of mIR‑584 overexpression on HCC cell proliferation and invasion, respectively. The present study demonstrated that miR‑584 expression was reduced in HCC tissues and cell lines compared with normal controls. Clinical analysis indicated that decreased miR‑584 expression was significantly associated with tumor size, TNM stage and lymph node metastasis of patients with HCC. Additionally, resumption of miR‑584 expression inhibited proliferation and invasion of HCC cells. Mechanistically, it was demonstrated that miR‑584 can directly interact with the 3'‑untranslated regions of brain‑derived neurotrophic factor (BDNF) mRNA, and reduce its mRNA and protein levels in HCC cells. Furthermore, BDNF was upregulated in HCC tissues, and its level was inversely correlated with miR‑584 expression. Notably, restored BDNF expression antagonized the inhibitory effects of miR‑584 overexpression on HCC cells. In conclusion, miR‑584 may serve tumor‑suppressive roles in HCC by directly targeting BDNF, thus suggesting that miR‑584 may serve as a potential candidate for treatment of patients with this disease.

Highlights

  • Hepatocellular carcinoma (HCC) ranks as the sixth most prevalent malignancy and the third most common cause of cancer‐related mortality globally [1]

  • reverse transcription‐quantitative PCR (RT‐qPCR) analysis demonstrated that miR‐584 was significantly downregulated in HCC tissues compared with adjacent non‐cancerous tissues (P

  • An increasing number of studies have demonstrated that numerous miRNAs are dysregulated in HCC; these aberrantly expressed miRNAs are contributing regulators of HCC formation and progression [27,28,29]; revealing the biological roles of miRNAs in HCC may identify new therapeutic targets and diagnosis methods

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Summary

Introduction

Hepatocellular carcinoma (HCC) ranks as the sixth most prevalent malignancy and the third most common cause of cancer‐related mortality globally [1]. HCC morbidity has significantly increased, the phenotype caused by hepatitis B or C virus infection [4]. The major therapeutic interventions for patients with HCC include surgical resection, radiotherapy, chemotherapy and molecular targeted therapy [5]. Despite the significant advancements in diagnosis and therapy, treatment outcomes of patients with HCC remain unsatisfactory, with a 5‐year survival rate of

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