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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. [ABSTRACT FROM AUTHOR]

Cancer stem cells are undifferentiated cancer cells that have self‐renewal ability, a high tumorigenic activity, and a multilineage differentiation potential. MicroRNAs play a critical role in regulating gene expression during carcinogenesis. Here, we investigated the role of miR‐7 and the mechanism by which it is dysregulated in gastric cancer stem cells (GCSCs). The stem cell marker, CD44, was used to sort GCSCs by fluorescence‐activated cell sorting. We found that CD44 (+) cells have higher invasiveness and form more number of sphere colonies than CD44 (−) cells. Quantitative real‐time polymerase chain reaction (PCR) revealed that the miR‐7‐5p expression was remarkably downregulated in GCSCs but was significantly increased in the methionine‐deprived medium. The downregulation of miR‐7‐5p results from the increased DNA methylation in the promoter region using the methylation‐specific PCR. Overexpression of miR‐7‐5p reduced the formation of colony and decreased the invasion of GCSCs through targeting Smo and Hes1 and subsequent repressing Notch and Hedgehog signaling pathways in vitro. Notably, upregulating miR‐7‐5p inhibited the growth of tumor in the xenograft model. Hence, these data demonstrated that miR‐7‐5p represses GCSC invasion through inhibition of Smo and Hes1, which provides a potential therapeutic target of gastric cancer treatment. [ABSTRACT FROM AUTHOR]