Transfer of LncRNA CRNDE in TAM‐derived exosomes is linked with cisplatin resistance in gastric cancer

Abstract

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.

Identification of a Novel Immune-Related lncRNA CTD-2288O8.1 Regulating Cisplatin Resistance in Ovarian Cancer Based on Integrated Analysis

“…As previous research works reported, lncRNA SNHG7 has been widely reported in various cancers to promote M2 polarization, therefore enhancing drug resistance ( Zhang et al, 2021 ). Silencing lncRNA CRNDE in M2-exo reverses the promotional effect of M2-exo on cell proliferation in CDDP-treated gastric cancer cells ( Xin et al, 2021 ). Moreover, lnc-TALC could be transmitted to TAMs and promote M2 polarization of the microglia ( Li Z. et al, 2021 ).…”

Advances in the Application of Exosomes Identification Using Surface-Enhanced Raman Spectroscopy for the Early Detection of Cancers

“…Exosomal-derived long noncoding RNA (lncRNA) TMZ-associated lnc RNA in GBM recurrence (lnc-TALC) modulates the glioblastoma (GBM) microenvironment and reduces the sensitivity of GBM to temozolomide chemotherapy, targeting exosomal-lnc-TALC may overcome TMZ resistance in GBM ( Li et al, 2021b ). Lnc RNA colorectal neoplasia differentially expressed (lnc-CRNDE) is highly expressed in tumor-associated macrophages (TAM) of gastric cancer (GC) patients, and CRNDE can be transferred from M2-polarized macrophages to GC cells via exosomal form and further promote GC cell proliferation and inhibit cisplatin resistance in GC cells ( Xin et al, 2021 ).…”

Potential Biological Roles of Exosomal Long Non-Coding RNAs in Gastrointestinal Cancer

“…In in vitro experiments, the expression level of lncRNA CRNDE was overexpressed in M2-polarized macrophage-derived exosomes (M2-exo) and it was encapsulated into exosomes to be transferred from M2 macrophages to GC cells. Studies showed that after GC cells are treated with M2-exo of silenced CRNDE, their cisplatin sensitivity was significantly enhanced ( Xin et al, 2021 ). Collectively, exosomal lncRNA may help clarify the underlying molecular mechanisms of therapeutic resistance in gastrointestinal cancer and provide promising therapeutic strategies.…”