Journal
EMBO REPORTS
Volume 22, Issue 12, Pages -Publisher
WILEY
DOI: 10.15252/embr.202052124
Keywords
cisplatin resistance; exosome; gastric cancer; LncRNA CRNDE; tumor-associated macrophages
Categories
Funding
- National Natural Science Foundation of China [81872480, 81760549, 81560492]
- Jiangxi Province Academic and Technical Leaders Training Program for Major Disciplines (Leading Talents Program)
Ask authors/readers for more resources
This study highlights the crucial role of LncRNA CRNDE in cisplatin resistance of gastric cancer cells, showing that CRNDE is transferred from M2 macrophages to GC cells via exosomes, regulating PTEN ubiquitination. This suggests that targeting CRNDE-mediated pathways may enhance chemotherapy sensitivity in gastric cancer.
This study explores the role of the long noncoding RNA (LncRNA) CRNDE in cisplatin (CDDP) resistance of gastric cancer (GC) cells. Here, we show that LncRNA CRNDE is upregulated in carcinoma tissues and tumor-associated macrophages (TAMs) of GC patients. In vitro experiments show that CRNDE is enriched in M2-polarized macrophage-derived exosomes (M2-exo) and is transferred from M2 macrophages to GC cells via exosomes. Silencing CRNDE in M2-exo reverses the promotional effect of M2-exo on cell proliferation in CDDP-treated GC cells and homograft tumor growth in CDDP-treated nude mice. Mechanistically, CRNDE facilitates neural precursor cell expressed developmentally downregulated protein 4-1 (NEDD4-1)-mediated phosphatase and tensin homolog (PTEN) ubiquitination. Silencing CRNDE in M2-exo enhances the CDDP sensitivity of GC cells treated with M2-exo, which is reduced by PTEN knockdown. Collectively, these data reveal a vital role for CRNDE in CDDP resistance of GC cells and suggest that the upregulation of CRNDE in GC cells may be attributed to the transfer of TAM-derived exosomes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available