Shan Jie, Pu Junxia, Chen Xiaohao, Zhang Yeni, Li Jinling, Qin Liumei, Shi Junhao, Zhou Lv, Deng Yibin
The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China.
Graduate School of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China.
Clin Exp Med. 2025 Feb 1;25(1):47. doi: 10.1007/s10238-025-01573-7.
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.
越来越多的研究表明,环状RNA(circRNA)在癌症的进展和发展中起主要作用。在此,我们研究了环状RNA 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)中的作用。采用肝癌细胞系的体外功能试验(细胞计数试剂盒8、TUNEL、划痕伤口愈合和侵袭试验)以及裸鼠皮下肿瘤的体内分析,来评估circACTN4对肝癌增殖的影响。利用荧光素酶报告基因试验以及对肝癌组织中circACTN4转录本的定量逆转录PCR研究,评估了circACTN4、微小RNA(miR)-424-5p和非SMC凝聚蛋白I复合体亚基G(NCAPG)之间的相互作用。研究结果表明,circACTN4在肝癌中高表达,促进肝癌细胞增殖,同时抑制其凋亡,且与预后不良相关。从机制上讲,circACTN4作为miR-424 5p的竞争性内源RNA,调控NCAPG水平并启动Wnt/β-连环蛋白信号通路,进而影响肝癌中的EMT机制。根据我们的研究,circACTN4/miR-424 5p/NCAPG轴可能是治疗肝癌的一个有吸引力的候选靶点。