LSD1 deletion represses gastric cancer migration by upregulating a novel miR-142-5p target protein CD9. (September 2020)

• Record Type: Journal Article
• Authors: Zhao, Li-Juan; Fan, Qi-Qi; Li, Ying-Ying; Ren, Hong-Mei; Zhang, Ting; Liu, Shuan; Maa, Mamun; Zheng, Yi-Chao; Liu, Hong-Min
• Is Part Of: Pharmacological research. Volume 159(2020)
• Publication Date: 2020-09
• Subjects: LSD1 Histone lysine specific demethylase 1 -- GC Gastric cancer -- EMT Epithelial-mesenchymal transition -- RISC RNA-induced silencing complex -- AGO2 Argonaute RISC Catalytic Component 2 -- ncRNAs Non-coding RNAs -- dsRNA Double strand RNA -- IFN Interferon -- pri-miRNAs Primary miRNAs -- pre-miRNAs Precursor miRNAs -- miRISC miRNA-induced silencing complex -- EVs Extracellular vesicles -- sEVs Small extracellular vesicles -- MVB Multivesicular bodies -- TEM Transmission electron microscope -- NTA Nanoparticle tracking analysis -- UC Ultracentrifugation -- KO Knockout -- HE staining Hematoxylin-eosin staining -- IHC Immunohistochemistry -- RPMI 1640 Roswell Park Memorial Institute 1640 -- RIPA Radio immunoprecipitation assay -- PBS Phosphate buffer saline; LSD1 -- miR142-5p -- CD9 -- Gastric cancer -- Migration -- Small extracellular vesicles; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2020.104991
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Highlights: LSD1 is a promoter in gastric cancer migration. LSD1 deletion suppresses gastric cancer migration by decreasing intracellular miR-142−5p. Migration suppressor CD9 is a new target of miR-142−5p. Secretion of miR-142−5p using sEVs as vehicles contributes to decreased amount of intracellular miR-142−5p. Abstract: 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.