Abstract

Circular RNAs (circRNAs) play an important role in the tumorigenesis of hepatocellular carcinoma (HCC), but their specific functions in HCC remain largely unknown. Using bioinformatics analysis, we have found that the expression of circRNA hsa_circ_0003141 is significantly increased in HCC tissues. Ubiquitin-associated protein 2 (UBAP2) is the parent gene for hsa_circ_0003141, and its high expression correlates with poor overall survival rates in HCC patients. In addition, our results show that miR-1827 is a binding target of hsa_circ_0003141, and indicate that hsa_circ_0003141 regulates UBAP2 expression by sponging miR-1827 in HCC cells. Downregulation of hsa_circ_0003141 suppresses UBAP2 expression, induces apoptosis, and inhibits proliferation and invasion by HCC Huh-7 cells. Importantly, downregulation of hsa_circ_0003141 inhibits tumorigenesis in a xenograft mouse model of HCC. Together, our results indicate that hsa_circ_0003141 functions as an oncogene in HCC cells, and suggest that the hsa_circ_0003141/miR-1827/UBAP2 axis might represent a novel therapeutic option for the treatment of HCC.

Highlights

  • Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancer, and is the third leading cause of cancer-related deaths in the world [1, 2]

  • A total of 287 DEcircRNAs were identified from the GSE94508 dataset; 251 were downregulated and 36 were upregulated

  • CircRNAs may serve as disease-specific biomarkers for disease diagnosis [20], and play a critical role in hepatocellular carcinoma (HCC) [21]

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Summary

Introduction

Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancer, and is the third leading cause of cancer-related deaths in the world [1, 2]. One of the major risk factors for HCC is chronic liver infection caused by hepatitis B or C virus (HBV or HCV) [3]. To improve diagnosis and prognosis of patients with HCC, it is critical to identify novel HCC biomarkers. Circular RNAs (circRNAs) are non-coding RNAs that exist mainly in the cytoplasm [7]. They lack 5′-3′ ends and polyadenylated tail, and form covalently closed loops [8]. CircRNAs regulate target mRNAs by acting as miRNA sponges [13]

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