Abstract
Circular RNAs (circRNAs) are a class of non-coding RNAs with a loop structure; however, their functions remain largely unknown. Growing evidence suggests that circRNAs play a pivotal role in the progression of malignant diseases. However, the expression profiles and function of circRNAs in hepatocellular carcinoma (HCC) remain unclear. We investigated the expression of microtubule-associated serine/threonine kinase 1 (MAST1) circRNA (circMAST1) in HCC and healthy tissues using bioinformatics, quantitative real-time PCR (qRT-PCR), and fluorescence in situ hybridization. Luciferase reporter assays were performed to assess the interaction between circMAST1 and miR-1299. Proliferation assays, colony formation assays, flow cytometry, transwell assays, and western blotting were also performed. A mouse xenograft model was also used to determine the effect of circMAST1 on HCC growth in vivo. CircMAST1 was upregulated in HCC tissues and cell lines; silencing via small interfering RNA inhibited migration, invasion, and proliferation of HCC cell lines in vitro as well as tumor growth in vivo. Furthermore, the expression of circMAST1 was positively correlated with catenin delta-1 (CTNND1) and negatively correlated with microRNA (miR)-1299 in HCC clinical samples. Importantly, circMAST1 sponged miR-1299 to stabilize the expression of CTNND1 and promoted tumorigenic features in HCC cell lines. We found that circMAST1 may serve as a novel biomarker for HCC. Moreover, circMAST1 elicits HCC progression by sponging miRNA-1299 and stabilizing CTNND1. Our data provide potential options for therapeutic targets in patients with HCC.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors globally and constitutes the third leading cause of cancer-related deaths worldwide[1]
Our study demonstrated that circMAST1 functions as a tumor promoter and induces HCC cancer cell proliferation and invasion through the miR-1299/catenin delta-1 (CTNND1) axis, suggesting that circMAST1 is a potential biomarker and therapeutic target for HCC
This is supported by our findings: (1) circMAST1 is highly expressed in HCC tissues, and HCC cell lines (e.g., HepG2 and HCCLM3); (2) silencing circMAST1 in a murine xenograft model significantly reduces the growth of HCC; (3) circMAST1 is likely required to sustain the cell cycle progression, proliferation, migration, and invasion of HCC cell lines; (4) circMAST1 is a miR-1299 sponge, and silencing circMAST1 inhibits cell growth significantly; (5) circMAST1 sponges miR-1299 to promote CTNND1 expression and is required to sustain cancer progression
Summary
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors globally and constitutes the third leading cause of cancer-related deaths worldwide[1]. In 2017, HCC, the 5-year survival rate of patients with this disease remains low[3]. Surgery is the most common intervention for patients with HCC, but most patients with multifocal development and distant metastases are ineligible for curative surgical treatment[4]. A deeper understanding of the molecular mechanisms underlying HCC progression is of paramount importance. Circular RNAs (circRNAs) are a newly discovered type of non-coding RNAs5,6. Unlike canonical linear RNAs, Official journal of the Cell Death Differentiation Association
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