Circ-EIF3I Promotes Hepatocellular Carcinoma Progression Through Modulating miR-361-3p/DUSP2 Axis.

DNA and cell biology Pub Date : 2024-05-01 Epub Date: 2024-03-22 DOI:10.1089/dna.2023.0400
Lingna Ni, Qianqian Gao, Qiu Zhao, Kejun Dai, Mingming Jin, Cong Fu, Min Xiao, Wenyu Zhu, Yanzhi Bi
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Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant cancers globally. Circular RNAs (circRNAs) have been implicated in the development of HCC. Previous studies have confirmed that circ-EIF3I plays an important role in the progress of lung cancer. Nevertheless, the biological functions of circ-EIF3I and the underlying mechanisms by which they regulate HCC progression remain unclear. In this study, the regulatory mechanism and targets were studied with bioinformatics analysis, luciferase reporting analysis, transwell migration, Cell Counting Kit-8, and 5-Ethynyl-2'-deoxyuridine analysis. In addition, in vivo tumorigenesis and metastasis assays were employed to evaluate the roles of circ-EIF3I in HCC. The result shows that the circ-EIF3I expression was increased in HCC cell line, which means that circ-EIF3I plays a role in the progression of HCC. Downregulation of circ-EIF3I suppressed HCC cells' proliferation and migration in both in vivo and in vitro experiments. Bioinformatics and luciferase report analysis confirmed that both miR-361-3p and Dual-specificity phosphatase 2 (DUSP2) were the downstream target of circ-EIF3I. The overexpression of DUSP2 or inhibition of miR-361-3p restored HCC cells' proliferation and migration ability after silence circ-EIF3I. Taken together, our study found that downregulation of circ-EIF3I suppressed the progression of HCC through miR-361-3p/DUSP2 Axis.

Circ-EIF3I 通过调节 miR-361-3p/DUSP2 轴促进肝细胞癌进展
肝细胞癌(HCC)是全球最常见的恶性癌症之一。环状 RNA(circRNA)被认为与 HCC 的发展有关。先前的研究证实,环状 EIF3I 在肺癌的进展过程中发挥着重要作用。然而,circ-EIF3I的生物学功能及其调控HCC进展的内在机制仍不清楚。本研究通过生物信息学分析、荧光素酶报告分析、transwell迁移、细胞计数试剂盒-8和5-乙炔基-2'-脱氧尿苷分析,对其调控机制和靶点进行了研究。此外,还采用了体内肿瘤发生和转移实验来评估 circ-EIF3I 在 HCC 中的作用。结果表明,circ-EIF3I在HCC细胞系中的表达增加,这意味着circ-EIF3I在HCC的进展过程中发挥作用。在体内和体外实验中,下调 circ-EIF3I 可抑制 HCC 细胞的增殖和迁移。生物信息学和荧光素酶报告分析证实,miR-361-3p和双特异性磷酸酶2(DUSP2)都是circ-EIF3I的下游靶标。过表达DUSP2或抑制miR-361-3p可恢复HCC细胞在沉默circ-EIF3I后的增殖和迁移能力。综上所述,我们的研究发现,下调circ-EIF3I可通过miR-361-3p/DUSP2轴抑制HCC的进展。
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