Hsa_circ_0011385 knockdown represses cell proliferation in hepatocellular carcinoma

Hao Lu,Xinchen Yang,Jun Xie,Shikun Yang,Wenjie Yang,Yang Ji,Yunfei Duan,Min Li,Chuangye Ni,Chuanyong Zhang,Yunjie Lu

doi:10.1038/s41420-021-00664-0

Abstract

Circular RNAs (circRNAs), continuous loops of single-stranded RNA, regulate gene expression during the development of various cancers. However, the function of circRNAs in hepatocellular carcinoma (HCC) is rarely discussed. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the mRNA levels of circ_0011385, miR-361-3p, and STC2 in 96 pairs of HCC tissues (tumor tissues and adjacent normal tissues), HCC cell lines, and L02 (human normal liver cell line) cells. The relationships between circ_0011385 expression and clinical features of HCC were evaluated. Functional experiments in vitro or in vivo were used to evaluate the biological function of circ_0011385. Bioinformatics analysis was performed to predict miRNAs and mRNAs sponged by circ_0011385. RNA immunoprecipitation (RIP) and dual-luciferase reporter gene assays were used to elucidate the interactions among circ_0011385, miR-361-3p, and STC2 (stanniocalcin 2). ChIP and dual-luciferase reporter gene assays were used to identify the upstream regulator of circ_0011385. High expression of circ_0011385 was observed in HCC tissues and cell lines and was significantly associated with tumor size, TNM stage, and prognosis. In addition, inhibition of circ_0011385 expression prevented the proliferation of HCC cells in vitro and in vivo. Circ_0011385 sponged miR-361-3p, thereby regulating the mRNA expression of STC2. In addition, the transcription of circ_0011385 was regulated by SP3. Circ_0011385 knockdown suppressed cell proliferation and tumor activity in HCC. Circ_0011385 may therefore serve as a new biomarker in the diagnosis and treatment of HCC.

Highlights

Hepatocellular carcinoma (HCC) is the third most common cancer in men worldwide [1, 2]
Circ_0011385 is upregulated in HCC tissues and cells The abnormally expressed circRNAs in HCC tissues were screened from GSE97332 data
To demonstrate the clinical significance of the upregulation of circ_0011385, we analyzed the clinicopathological characteristics of patients with HCC

Summary

Introduction

Hepatocellular carcinoma (HCC) is the third most common cancer in men worldwide [1, 2]. The incidence of HCC ranks third among all cancers in China, and HCC is responsible for more than 50% of new cases and deaths worldwide [3]. HCC can be caused by HBV infection and cirrhosis [4]. In the past few decades, substantial efforts have attempted to improve the prognosis of HCC. Many novel alternative therapies have been developed, surgical resection remains the main choice for HCC [5]. The 5-year survival rate remains very low (

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Conclusion