This study focused on the role of methionine (MET) in the autophagy of gastric cancer stem cells (GCSCs) and aims to elaborate its regulatory mechanism. In the present study, the GCSCs were isolated from human gastric cancer cell lines using an anti-CD44 antibody, and then cultured in MET homocysteine (HCY) or METHCY medium. In METHCYtreated GCSCs, autophagy was suppressed, the methylation and phosphorylation of RAB37 were elevated, and miR-200b expression was down-regulated. Lentiviral vector (LV-) carrying methionine-γ lyase (an enzyme that could specifically lyse MET; Metase) promoted autophagy, reduced the methylation and phosphorylation of RAB37, and up-regulated miR-200b expression in METHCY-treated GCSCs. Then, we found that miR-200b suppressed the expression of protein kinase C α (PKCα), a protein that could inactivate RAB37 through promoting its phosphorylation. LV-Metase down-regulated RAB37 phosphorylation via miR-200b/PKCα, thus promoting the RAB37-mediated autophagy and suppressing cell viability in METHCYtreated GCSCs. Finally, the study proved that LV-Metase treatment inhibited tumor growth through up-regulating RAB37 expression. In conclusion, MET suppressed RAB37 expression via enhancing its methylation and suppressed RAB37 activity via miR-200b/PKCα axis, thus repressing RAB37-mediated autophagy in GCSCs. The supplementation of Metase lysed MET, thus inducing the autophagy of GCSCs and inhibiting tumor growth.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646514PMC
http://dx.doi.org/10.1080/15384101.2020.1814044DOI Listing

Publication Analysis

Top Keywords

gastric cancer
12
methylation phosphorylation
12
phosphorylation rab37
12
autophagy gastric
8
cancer stem
8
stem cells
8
rab37
8
methcytreated gcscs
8
mir-200b expression
8
rab37-mediated autophagy
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!