乙酰化
脂质代谢
转移
癌症研究
组蛋白
脂肪酸代谢
癌症
肺癌
癌细胞
化学
新陈代谢
细胞
生物
细胞生物学
生物化学
内科学
基因
医学
遗传学
作者
Yingmeng Ni,Ying Yang,Jingjing Ran,Lu Zhang,Menglin Yao,Zhiqiang Liu,Li Zhang
标识
DOI:10.1016/j.freeradbiomed.2020.10.009
摘要
Metabolic reprogramme was a key characteristic of malignant tumors. Increased evidences indicated that besides Warburg effect (abnormal glucose metabolism), abnormal lipid metabolism played more and more important in progression and metastasis of malignant tumors. MiR-15a-5p could inhibit development of lung cancer, while its regulating mechanism, especially the role in lipid metabolism still remained unclear. In this study, we confirmed that miR-15a-5p inhibited proliferation, migration and invasion of lung cancer cells. The online analysis of Mirpath v.3 predicted that miR-15a-5p was closely associated with fatty acid synthesis and lipid metabolism. In vitro cell experiments revealed that miR-15a-5p significantly suppressed fatty acid synthesis of lung cancer cells by inhibiting acetate uptake. Extensive analysis indicated that miR-15a-5p could suppress acetyl-CoA activity and decrease histone H4 acetylation by inhibiting ACSS2 expression. In addition, we also observed that ACSS2 located in nucleus under hypoxic conditions, while miR-15a-5p could be transported into nucleus to inhibit the function of ACSS2. Our study unveiled a novel mechanism of miR-15a-5p in inhibiting metastasis of lung cancer cells by suppressing lipid metabolism via suppression of ACSS2 mediated acetyl-CoA activity and histone acetylation.
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