CircRNA circACTN4 Promotes the Progression of Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma by Targeting the miR-424-5p/NCAPG/Wnt Axis.

IF 3.5 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Clinical and Experimental Medicine Pub Date : 2025-02-01 DOI:10.1007/s10238-025-01573-7
Jie Shan, Junxia Pu, Xiaohao Chen, Yeni Zhang, Jinling Li, Liumei Qin, Junhao Shi, Lv Zhou, Yibin Deng
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Abstract

Growing research reveals that circular RNAs (circRNAs) play a major part in the progression and development of cancer. Here, we investigated the oncogenic function and regulatory mechanisms of the circRNA circACTN4 in hepatocellular carcinoma (HCC), particularly in the tumor epithelial-mesenchymal transition (EMT). In vitro functional assays (Cell Counting Kit 8, TUNEL, scratch wound healing, and invasion assays) of HCC cell lines, alongside in vivo analyses of subcutaneous tumors in nude model mice, were employed to assess the impact of circACTN4 on HCC proliferation. Interactions concerning circACTN4, microRNA (miR)-424-5p, and non-SMC condensing I complex subunit G (NCAPG) have been assessed deploying luciferase reporter assays and also quantitative reverse transcription PCR investigation of circACTN4 transcripts in HCC tissues. Findings indicated a high expression of circACTN4 in HCC, promoted proliferation, while inhibiting apoptosis of HCC cells, and correlated with poor prognosis. Mechanistically, circACTN4 served as a rival internal RNA for miR-424 5p, controlling NCAPG level and initiating the Wnt/β-catenin signaling routes, which in turn impacted the EMT machinery in HCC. According to our surveys, the circACTN4/miR-424 5p/NCAPG axis could be an intriguing candidate for therapy to address the treatment of HCC.

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CircRNA circACTN4通过靶向miR-424-5p/NCAPG/Wnt轴促进肝细胞癌上皮-间质转化的进展
越来越多的研究表明,环状rna (circRNAs)在癌症的进展和发展中起着重要作用。在这里,我们研究了circRNA circACTN4在肝细胞癌(HCC)中的致癌功能和调控机制,特别是在肿瘤上皮-间质转化(EMT)中。通过肝癌细胞系的体外功能测定(细胞计数试剂盒8、TUNEL、划伤愈合和侵袭试验),以及裸鼠模型皮下肿瘤的体内分析,评估circACTN4对HCC增殖的影响。利用荧光素酶报告基因测定和circACTN4转录物的定量反转录PCR研究,评估了circACTN4、microRNA (miR)-424-5p和非smc冷凝I复合体亚基G (NCAPG)之间的相互作用。研究结果表明,circACTN4在HCC中高表达,促进细胞增殖,抑制细胞凋亡,与预后不良相关。在机制上,circACTN4作为mir - 4245p的竞争性内部RNA,控制NCAPG水平并启动Wnt/β-catenin信号通路,进而影响HCC中的EMT机制。根据我们的调查,circACTN4/miR-424 5p/NCAPG轴可能是解决HCC治疗的一个有趣的候选疗法。
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来源期刊
Clinical and Experimental Medicine
Clinical and Experimental Medicine 医学-医学:研究与实验
CiteScore
4.80
自引率
2.20%
发文量
159
审稿时长
2.5 months
期刊介绍: Clinical and Experimental Medicine (CEM) is a multidisciplinary journal that aims to be a forum of scientific excellence and information exchange in relation to the basic and clinical features of the following fields: hematology, onco-hematology, oncology, virology, immunology, and rheumatology. The journal publishes reviews and editorials, experimental and preclinical studies, translational research, prospectively designed clinical trials, and epidemiological studies. Papers containing new clinical or experimental data that are likely to contribute to changes in clinical practice or the way in which a disease is thought about will be given priority due to their immediate importance. Case reports will be accepted on an exceptional basis only, and their submission is discouraged. The major criteria for publication are clarity, scientific soundness, and advances in knowledge. In compliance with the overwhelmingly prevailing request by the international scientific community, and with respect for eco-compatibility issues, CEM is now published exclusively online.
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