State Key Laboratory of Esophageal Cancer Prevention & Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Key Laboratory of Henan Province for Drug Quality and Evaluation, Institute of Drug Discovery and Development, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China.
State Key Laboratory of Esophageal Cancer Prevention & Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Key Laboratory of Henan Province for Drug Quality and Evaluation, Institute of Drug Discovery and Development, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China.
Pharmacol Res. 2020 Sep;159:104991. doi: 10.1016/j.phrs.2020.104991. Epub 2020 Jun 3.
LSD1 (histone lysine specific demethylase 1) takes part in the physiological process of cell differentiation, EMT (epithelial-mesenchymal transition) and immune response. In this study, we found LSD1 expression in metastatic gastric cancer tissues was significantly higher than that in normal tissues. Furthermore, LSD1 deletion was found to suppress gastric cancer migration by decreasing intracellular miR-142-5p, which further led to the upregulation of migration suppressor CD9, a newly identified target of miR-142-5p. While LSD1 was reported as a demethylase of H3K4me1/2, H3K9me1/2 and several non-histone proteins, this is a new evidence for LSD1 as a functional regulator of miRNA. On the other hand, our data suggested that promoting the secretion of miR-142-5p using small extracellular vesicles as vehicles is a new mechanism for LSD1 abrogation to down-regulate intracellular miR-142-5p. Taken together, this study uncovered a new mechanism for LSD1 that can contribute to gastric cancer migration by facilitating miR-142-5p to target CD9.
LSD1（组蛋白赖氨酸特定去甲基酶 1）参与细胞分化、EMT（上皮-间质转化）和免疫反应等生理过程。在本研究中，我们发现 LSD1 在转移性胃癌组织中的表达明显高于正常组织。此外，我们发现 LSD1 的缺失通过降低细胞内 miR-142-5p 的表达抑制了胃癌的迁移，从而进一步上调了 miR-142-5p 的新靶标迁移抑制因子 CD9。虽然 LSD1 被报道为 H3K4me1/2、H3K9me1/2 和几种非组蛋白蛋白的去甲基酶，但这是 LSD1 作为 miRNA 功能调节剂的新证据。另一方面，我们的数据表明，使用小细胞外囊泡作为载体促进 miR-142-5p 的分泌是 LSD1 缺失下调细胞内 miR-142-5p 的一种新机制。综上所述，本研究揭示了 LSD1 的一种新机制，通过促进 miR-142-5p 靶向 CD9，有助于胃癌的迁移。
