1. Academic Validation
  2. miR-15a-5p inhibits metastasis and lipid metabolism by suppressing histone acetylation in lung cancer

miR-15a-5p inhibits metastasis and lipid metabolism by suppressing histone acetylation in lung cancer

  • Free Radic Biol Med. 2020 Dec;161:150-162. doi: 10.1016/j.freeradbiomed.2020.10.009.
Yinyun Ni 1 Ying Yang 1 Jingjing Ran 1 Lu Zhang 2 Menglin Yao 1 Zhiqiang Liu 1 Li Zhang 3
Affiliations

Affiliations

  • 1 Precision Medicine Research Center, West China Hospital of Sichuan University, Chengdu, 610041, China.
  • 2 West China-Washington Mitochondria and Metabolism Center, West China Hospital of Sichuan University, Chengdu, 610041, China.
  • 3 Precision Medicine Research Center, West China Hospital of Sichuan University, Chengdu, 610041, China; Laboratory of Pathology, West China Hospital of Sichuan University, Chengdu, 610041, China. Electronic address: zhangli7375@scu.edu.cn.
Abstract

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.

Keywords

ACSS2; Acetylation; Lipid metabolism; Lung cancer; Metastasis; miR-15a-5p.

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