circSOX4 Enhances Hepatocellular Carcinoma Progression via miR-218-5p/YY1 Signaling

Abstract

Liver cancer ranks fifth leading malignancy in incidence and third in mortality worldwide. Recently, its comprehensive treatment has greatly progressed; however, the prognosis is still poor due to difficulties in early diagnosis, high recurrence and metastasis rates, and lack of specific treatment. The search for new molecular biological factors that target the early diagnosis of cancer, predict recurrence, evaluate treatment efficacy, and identify high-risk individuals and specific therapeutic targets during follow-up becomes a great urgent task. circSOX4 is upregulated in lung cancer and plays the role of oncogene. This study attempted to assess circSOX4’s role in hepatocellular carcinoma (HCC). HCC tissues and cells were collected to measure circSOX4 level by qRT-PCR, cell behaviors by CCK-8 assay and Transwell assay, and relationship between circSOX4 and downstream targets by dual-luciferase gene assay and RIP. circSOX4 was upregulated in HCC tissue and cell lines, and its level was correlated with reduced patient survival. Interestingly, circSOX4 knockdown reduced HCC behaviors, glucose consumption, and lactate production. Furthermore, circSOX4 knockdown resulted in decreased in vivo tumor growth. circSOX4 was confirmed to target miR-218-5p, and the effect of circSOX4 downregulation on inhibiting tumor growth was diminished after miR-218-5p inhibition or YY1 overexpression in HCC cells. circSOX4 expression is closely associated with HCC through miR-218-5p and YY1-dependent pathways and may be a target and marker for HCC.