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Xin, Lin; Zhou, Li‐Qiang; Liu, Chuan; Zeng, Fei; Yuan, Yi‐Wu; Zhou, Qi; Li, Shi‐Hao; Wu, You; Wang, Jin‐Liang; Wu, Deng‐Zhong; Lu, Hao
EMBO reports, 06 December 2021, Letnik: 22, Številka: 12Journal Article
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. SYNOPSIS LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes, suppressing PTEN expression in GC cells. The latter leads to a reduced sensitivity of GC cells to cisplatin. LncRNA CRNDE is enriched in TAMs of GC patients. LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes in vitro. CRNDE facilitates NEDD4‐1‐mediated PTEN ubiquitination in GC cells. Exosomal transfer of LncRNA CRNDE is linked to cisplatin resistance in GC cells caused by reduced PTEN levels. LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes, suppressing PTEN expression in GC cells. The latter leads to a reduced sensitivity of GC cells to cisplatin.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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