Abstract

Purpose Hepatocellular carcinoma (HCC), a malignant tumor that exists worldwide, has a high morbidity and mortality rate. Previous studies have reported that lncRNA NR2F1-AS1 plays a critical role in several cancers. Here, we aimed to investigate the biological function of NR2F1-AS1 and its molecular mechanism in the migration and invasion of HCC. Methods Quantitative real-time PCR (qRT-PCR) was performed to analyze NR2F1-AS1 expression in HCC. The biological function was investigated by transwell invasion and migration assays. The protein level was identified by Western blot. In addition, the downstream targets of NR2F1-AS1 and miR-642a were confirmed by luciferase reporter assays. Results NR2F1-AS1 was significantly upregulated in HCC and associated with the poor prognosis of HCC patients. Biological function experiments revealed that the silence of NR2F1-AS1 suppressed cell invasion and migration in HCC. More importantly, NR2F1-AS1 directly interacted with miR-642a and negatively regulated miR-642a. DEK was the target of miR-642a, and NR2F1-AS1 positively regulated DEK expression by suppressing miR-642a. Conclusion Taken together, it is the first time we discovered the interaction of NR2F1-AS1 with miR-642a in modulating HCC cell invasion and migration.

Highlights

  • Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, which initiates in hepatocytes and has a high mortality rate [1, 2]

  • Results displayed that NR2F1-AS1 was highly expressed in HCC tumor tissues when compared to adjacent nontumor tissues (Figure 1(a)). e median value of NR2F1-AS1 expression was used as the cutoff point to divide NR2F1-AS1 expression into high and low expression of NR2F1-AS1

  • LncRNA profile analysis and functional analysis of various types of cancer have provided more and more evidence that Long noncoding RNAs (lncRNAs) plays a critical role in tumor growth and development [14]. lncRNA is considered to be a new diagnostic biomarker, effective prognostic predictor, and attractive therapeutic target for HCC through interactions with cellular macromolecules, such as proteins and mRNAs [15, 16]. us, it is critically called for to understand the molecular mechanism of lncRNAs in HCC progression

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Summary

Introduction

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, which initiates in hepatocytes and has a high mortality rate [1, 2]. Long noncoding RNAs (lncRNAs), as a new epigenetic regulatory molecule, have received wide attention in various cellular and biological processes. LncRNAs have been found to be critical regulators in HCC [5, 6]. LncRNA OTUD6B-AS1 was highly expressed in HCC and associated with HCC patients’ prognosis. A novel lncRNA, NR2F1 antisense RNA 1 (NR2F1-AS1), was functionally identified [9]. Mounting evidence has discovered that NR2F1-AS1 played a critical role in the development of various cancers, including colorectal cancer [10], breast cancer [11], and Journal of Oncology esophageal squamous cell carcinoma [12]. The biological role of NR2F1-AS1 and the detailed mechanism in HCC cell invasion and migration are yet to be explored

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