Abstract

Recent studies have investigated the modulatory roles of long non-coding RNAs in the onset and progression of liver cancer. The present study aimed to elucidate the role of lnc-GNAT1-1 in liver cancer development and to explore the underlying mechanisms. Quantitative real-time polymerase chain reaction was performed to measure the expression levels of lnc-GNAT1-1 in cancerous tissues from patients with liver cancer and in liver cancer cell lines. The proliferative ability and apoptotic rates of liver cancer cells were measured using the counting kit-8 (CCK-8), colony formation, and flow cytometry assays. The abilities to invade and migrate were measured using Transwell assays. Epithelial–mesenchymal transition (EMT)-related proteins, E-cadherin, N-cadherin, and vimentin, were measured using western blotting. A nude mouse model was injected with xenografts to evaluate tumor growth in vivo. Downregulation of lnc-GNAT1-1 was observed in cancerous tissues from patients with liver cancer and in liver cancer cell lines, and low expression levels of lnc-GNAT1-1 were related to advanced TNM stage. Lnc-GNAT1-1 knockdown promoted invasion, migration, and proliferation of liver cancer cells and inhibited apoptosis, while lnc-GNAT1-1 upregulation exerted the opposite effects. The expression levels of lnc-GNAT1-1 negatively correlated with in vivo tumor growth in a xenograft nude mouse model. Mechanistic experiments revealed that lnc-GNAT1-1 exerted anti-tumor effects in liver cancer cells by inhibiting EMT. In conclusion, this study suggests that lnc-GNAT1-1 suppresses liver cancer progression by modulating EMT.

Highlights

  • Liver cancer was the fourth leading cause of cancer death in 2018 (Bray et al, 2018)

  • We carried out Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) to measure the expression levels of lnc-GNAT1-1 in 42 paired normal–cancer liver tissues

  • Downregulation of lnc-GNAT1-1 was observed in the liver cancer cell lines (Huh7, QGY-7703, Hep3B, GSG7701, SMMC-7721) when compared with the normal liver cell line (LO2; Figure 1C)

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Summary

Introduction

Liver cancer was the fourth leading cause of cancer death in 2018 (Bray et al, 2018). It was one of the five leading causes of death in China (Zhou et al, 2019). Tremendous advances have been made in liver cancer treatment, including liver resection, radiofrequency and microwave ablation, liver transplantation, and chemotherapy. The early detection rate of human cancer has increased, and this has improved survival (Couri and Pillai, 2019). Liver cancer detected at advanced stages remains difficult to treat and survival rates remain low. It is essential to explore the molecular mechanisms underlying liver cancer initiation and progression to offer novel insights for treatment

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