Downregulation of lncRNA SBF2-AS1 inhibits hepatocellular carcinoma proliferation and migration by regulating the miR-361-5p/TGF-β1 signaling pathway.

Yan-Hui Wu,Wei Zhang,Wei-Xun Chen,Bin Yu,Xi Ai,Ya-Jie Shao,Wei Dong

doi:10.18632/aging.203248

Abstract

SBF2-AS1 is an oncogenic long non-coding RNA (lncRNA). However, its role and mechanism in hepatocellular carcinoma (HCC) is still not completely clear. The HepG2, Hep3B, Bel-7402 and HL-7702 cell lines were used in our experiments. The CCK-8 kit and EdU staining were applied to detect cell viability and multiplication. The wound healing and Boyden chamber cell migration assays were employed to test the migration ability of cells. The levels of TGF-β1 mRNA, lncRNA SBF2-AS1, and miR-361-5p were assessed by real-time PCR. TGF-β1 protein levels were evaluated by western blotting. The direct interaction between miR-361-5p and TGF-β1 was determined by luciferase reporter assays. A xenograft mouse model (XMM) was established to comprehensively study the effect and mechanisms of lncRNA SBF2-AS1. lncRNA SBF2-AS1 concentration in HCC cells exceeded that in a normal hepatocyte cell line. The downregulation of lncRNA SBF2-AS1 upregulated miR-361-5p levels in HCC cells. And, miR-361-5p negatively regulate TGF-β1 expression in HCC cells. The suppression of miR-361-5p attenuated the influence of lncRNA SBF2-AS1 downregulation on the viability, proliferation, and migration capability of HCC cells. Further, the downregulation of lncRNA SBF2-AS1 inhibited neoplasm growth in an XMM of HCC. Simultaneously, miR-361-5p was upregulated and TGF-β1 was downregulated after lncRNA SBF2-AS1 knocked down. In conclusion, downregulation of lncRNA SBF2-AS1 inhibits HCC proliferation and migration through the regulation of the miR-361-5p/TGF-β1 signaling pathway.

Highlights

Hepatocellular carcinoma (HCC) is considered one of the major causes of death worldwide, accounting for more than 600,000 deaths each year [1]
Level of long non-coding RNA (lncRNA) SBF2-AS1 increased in HCC cells
Compared to normal hepatocyte HL-7702 cells (Figure 1A), the data revealed that the level of lncRNA SBF2-AS1 was higher in both the HepG2 and Hep3B HCC cell lines

Summary

Introduction

Hepatocellular carcinoma (HCC) is considered one of the major causes of death worldwide, accounting for more than 600,000 deaths each year [1]. The diagnosis and treatment of HCC are still fraught with issues. Non-coding RNAs are emerging as new diagnostic and therapeutic agents in various diseases. Recent studies have focused on long non-coding RNAs (lncRNAs) in HCC. LncRNAs are aberrantly expressed in HCC tissues. 612 lncRNAs have been identified at different levels of HCC tissues [2]. Some lncRNAs are major factors in carcinogenesis and disease progression. This includes lncRNA homeobox A11 antisense (HOXA11-AS), which is upregulated in relevant cell lines and HCC tissues. The enhanced expression of this lncRNA can promote proliferation, invasion, and epithelial-mesenchymal transition (EMT)

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Results

Conclusion