淋巴管新生
下调和上调
转移
癌症研究
脂质代谢
癌症
血管生成
生物
癌基因
脂肪酸代谢
脂肪酸
医学
内科学
内分泌学
生物化学
细胞周期
基因
作者
Sheng Zhong,Quanwei Guo,Xiaona Chen,Xiaomin Luo,Yun Long,Tuotuo Chong,Ming Ye,Hong He,A.C.W. Lu,Keyi Ao,Minuo Yin,Aiqiang Xu,Xin Li,Yi Hao,Xiaoxiao Guo
摘要
The lipid synthesis of fatty acid (FA) represents a significant hallmark in the occurrence and progression of malignant tumor, which are associated with lymph node (LN) metastasis. Elucidation of the molecular mechanisms underlying LN metastasis could provide therapeutic strategies for cervical cancer (CCa). N6-Methyladenosine (m6A), the most prevalent and abundant RNA modification, exerts specific regulatory control over a series of oncogene expressions. This study demonstrated a clinical correlation between the upregulation of the m6A reader YTHDF3 and LN metastasis, thereby contributing to poor overall survival probability (OS) among CCa patients. The mechanistic investigation revealed that SREBF1 transcriptionally activated YTHDF3 expression by binding to its promoter. Functional experiments demonstrated that the upregulation of YTHDF3 significantly enhanced the in vitro proliferative, migratory, and invasive capacities of CCa cells, while also promoting lymphangiogenesis and facilitating LN metastasis in vivo. Mechanistically, the upregulation of LRP6 through YTHDF3-mediated m6A modification resulted in increased expression of FASN and ACC1, leading to both lipolysis of lipid droplets and synthesis of free fatty acid. Ultimately, this promoted fatty acid metabolism and enhanced LN metastasis by activating the LRP6-YAP-VEGF-C axis, which could induce lymphangiogenesis in CCa. Our study highlighted that YTHDF3 can serve as a promising therapeutic target and predictive biomarker for CCa patients with LN metastasis.
科研通智能强力驱动
Strongly Powered by AbleSci AI