LncRNA NEAT1 regulates HCV-induced Hepatocellular carcinoma by modulating the miR-9-BGH3 axis

Abstract

Chronic hepatitis C virus (HCV) infection is a leading cause of end-stage liver diseases, such as fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Several cellular entities, including paraspeckles and their related components, are involved in viral pathogenesis and cancer progression. NEAT1 lncRNA is a major component of paraspeckles that has been linked to several malignancies. In this study, analysis of the Cancer Genome Atlas (TCGA) database and validation in HCV-induced HCC tissue and serum samples showed significantly high expression of NEAT1 in patients with liver cancer. Moreover, we found that NEAT1 levels increased upon HCV infection. To further understand the mechanism of NEAT1-induced HCC progression, we selected one of its targets, miR-9–5 p, which regulates BGH3 mRNA levels. Interestingly, miR-9–5 p levels were downregulated upon HCV infection, whereas BGH3 levels were upregulated. Additionally, partial NEAT1 knockdown increased miR-9–5 p levels and decreased BGH3 levels, corroborating our initial results. BGH3 levels were also upregulated in HCV-induced HCC and TCGA tissue samples, which could be directly correlated with NEAT1 levels. As a known oncogene, BGH3 is directly linked to HCC progression mediated by NEAT1. We also found that NEAT1 levels remained upregulated in serum samples from patients treated with direct-acting antivirals (DAA), indicating that NEAT1 might be a molecular trigger that promotes HCC development. Collectively, these findings provide molecular insights into HCV-induced HCC progression via the NEAT1-miR-9-BGH3 axis.

Research progress of circulating non-coding RNA in diagnosis and treatment of hepatocellular carcinoma

“…The analysis of the TCGA database revealed that NEAT1 is expressed at high levels in patients with hepatitis C virus-induced HCC. Furthermore, there was no significant decrease in serum NEAT1 levels after antiviral treatment (111). This suggests that NEAT1 may play a role in triggering liver malignancy and could serve as a useful biomarker for early HCC diagnosis.…”

The role of competing endogenous RNA network in the development of hepatocellular carcinoma: potential therapeutic targets

“…TUG1 promoted SIX1 expression, increasing glycolysis and metastasis in HCC cells by interacting with miR-524–5p ( Lu et al, 2022a ) and activated the JAK/STAT3 pathway by targeting miR-144 ( Lv et al, 2018 ). Additionally, NEAT1 influenced HCC progression by modulating the miR-9-BGH3 axis ( Tripathi et al, 2022 ). Furthermore, the lncRNA CDKN2BAS/miR-153–5p/ARHGAP18 and RP11-386G11.10/miR-345–3p/HNRNPU networks, upregulated in HCC tissues, correlated with larger tumor size, advanced TNM stage, and poorer prognosis in patients ( Chen et al, 2018 ; Xu et al, 2022 ).…”

PSPC1 Binds to HCV IRES and Prevents Ribosomal Protein S5 Binding, Inhibiting Viral RNA Translation

“…The IRES comprises the first 24-40 nucleotides of the core coding region and domains II, III, and IV of the 5' UTR [1]. The propagation of HCV depends on host factors such as proteins, miRNAs, and lncRNAs [2][3][4]. It has been shown that several cellular proteins are required for HCV translation, such as Human La autoantigen (La), poly(rC)-binding protein 2 (PCBP2), and ribosomal protein S5 (RPS5) [5][6][7][8][9][10][11][12][13][14].…”