Yang Shude, Sun Yudi, Wang Ning, Yang Ziming, Xing Hao, Jia Jialin
Department of Plastic Surgery, The First Hospital of China Medical University, No.155 Nanjing North Street, Heping District, 110001, Shenyang, Liaoning Province, People's Republic of China.
Mol Cell Biochem. 2025 Feb;480(2):1155-1167. doi: 10.1007/s11010-024-05045-6. Epub 2024 Jun 15.
LncRNAs have been demonstrated to regulate biological processes in malignant tumors. In our previous study, we identified the immune-related LncRNA RNF144A-AS1 as a potential regulator in SKCM. However, its precise function and regulatory mechanism remain unclear. In this study, we observed upregulation of RNF144A-AS1 in SKCM and found that knockdown of RNF144A-AS1 suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition abilities of melanoma cells. Mechanistically, as a high-risk prognostic factor, RNF144A-AS1 regulated biological processes of SKCM by interacting with TAF15 through an RNA-binding protein-dependent (RBP-dependent) manner. Furthermore, we confirmed that TAF15 activated downstream transcriptional regulation of YAP1 to modulate malignant behaviors in melanoma cells. In vivo experiments revealed that knockdown of RNF144A-AS1 inhibited tumorigenic capacity of melanoma cells and exhibited promising therapeutic effects. Collectively, these findings highlight the significance of the RNF144A-AS1/TAF15/YAP1 axis in promoting malignant behaviors in SKCM and provide novel insights into potential prognostic biomarkers and therapeutic targets for this disease.
长链非编码RNA(lncRNAs)已被证明可调节恶性肿瘤中的生物学过程。在我们之前的研究中,我们确定免疫相关的lncRNA RNF144A-AS1是皮肤黑色素瘤(SKCM)中的一种潜在调节因子。然而,其确切功能和调节机制仍不清楚。在本研究中,我们观察到SKCM中RNF144A-AS1上调,并发现敲低RNF144A-AS1可抑制黑色素瘤细胞的增殖、迁移、侵袭和上皮-间质转化能力。机制上,作为一种高危预后因素,RNF144A-AS1通过RNA结合蛋白依赖性(RBP依赖性)方式与TAF15相互作用来调节SKCM的生物学过程。此外,我们证实TAF15激活YAP1的下游转录调控以调节黑色素瘤细胞中的恶性行为。体内实验表明,敲低RNF144A-AS1可抑制黑色素瘤细胞的致瘤能力,并显示出有前景的治疗效果。总的来说,这些发现突出了RNF144A-AS1/TAF15/YAP1轴在促进SKCM恶性行为中的重要性,并为该疾病的潜在预后生物标志物和治疗靶点提供了新的见解。