Abstract

MicroRNAs (MiRNAs), which regulate the gene expression leading to translational inhibition or mRNA degradation, are involved in carcinogenesis and tumor progression. Previous studies have demonstrated that miR-221 was one of the most consistent overexpressed miRNAs in several types of cancer. However, the role of miR-221 in human liver cancer progression is not yet fully elucidated. Levels of miR-221 and plant homeodomain finger 2 (PHF2) expressions in human hepatocellular carcinoma (HCC) tissues and cell lines were detected using western blotting and quantitative real-time PCR (qRT-PCR). Cell migration was studied using the transwell assays. A dual-luciferase reporter system was used to validate the target gene of miR-221. The results indicated that miR-221 promoted HCC cell migration. By performing subsequent systematic bioinformatic analyses, we found PHF2 was the target gene of miR-221 and the direct binding relationship was further validated by dual-luciferase reporter assay. In addition, lower expression of PHF2 promoted HCC cell migration and linked to worse overall survival in HCC patients. Finally, the negative correlation between miR-221 and PHF2 expression levels in HCC specimens was further confirmed. Taken together, our findings implied that miR-221 could be a potential candidate for the therapeutics of HCC metastasis.

Highlights

  • Hepatocellular carcinoma (HCC) is the fifth common cancer and third leading cause of cancer-related deaths worldwide, and it is considered to be one of the most common cancers with poor prognosis [1]

  • To investigate the mRNA level of miR-221 in HCC cell lines, quantitative real-time PCR (qRT-PCR) was performed and results demonstrated that the miR-221 mRNA levels in HCC cell lines were higher than human normal hepatocyte (HL-7702) (Figure 1(a))

  • We used HCC cells to examine the role of miR-221 on cell migration

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Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth common cancer and third leading cause of cancer-related deaths worldwide, and it is considered to be one of the most common cancers with poor prognosis [1]. Previous studies have considerably focused on study of DNA mutations and gene expression changes in HCC [2]. RNA mutations and change of mRNA transcription are correlated with the initiation and progression of HCC. MicroRNAs (miRNAs) are small noncoding RNAs with approximately 22 nucleotides that could play important regulatory roles in plants and animals by targeting mRNAs for translational suppression [3]. By modulating gene expression via posttranscriptional mechanisms, miRNAs are known as vital players in cell cycle, differentiation, apoptosis, and oncogenesis [5]. MiRNAs are identified to be correlated with the regulation of epithelial-mesenchymal transition and tumor metastasis by targeting important genes [6, 7]. MiR-221, which is encoded by human chromosome Xp11.3, is often abnormally expressed and associated with the regulation of oncogenes or tumor suppressive genes. Identification of the function of miR-221 and its targets could make a new access to cancer treatment

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