Exosomal lncRNA SNHG10 derived from colorectal cancer cells suppresses natural killer cell cytotoxicity by upregulating INHBC

作者：Yi‐Wen Huang, Yanbo Luo, Yanbo Luo, Wentao Ou, Yuanyuan Wang, Dong Dong, Xiaowen Peng, Yuqi Luo, Yuqi Luo · 发表于：Cancer Cell International · 年份：2021 · DOI：10.1186/s12935-021-02221-2 · 被引用次数：92 · 研究领域：Cancer-related molecular mechanisms research、Extracellular vesicles in disease、Ferroptosis and cancer prognosis

BACKGROUND: Exosome-mediated crosstalk between cancer cells and immune cells contributes to tumor growth. In this study, we investigated the mechanism underlying the exosome-mediated immune escape of colorectal cancer (CRC) cells from natural killer (NK) cells via the transfer of long noncoding RNAs (lncRNAs). METHODS: An epithelial-mesenchymal transition (EMT) model of SW480 cells was established by transforming growth factor beta (TGF-β), followed by the assessment of the effect of EMT-derived exosomes (EMT-exo) on the functions of NK cells. RNA sequencing was performed to identify exosomal lncRNAs and target genes. The function of exosomal lncRNAs in tumor growth was further verified in vivo. RESULTS: EMT-exo suppressed the proliferation, cytotoxicity, IFN-γ production, and perforin-1 and granzyme B secretion of NK cells. RNA sequencing revealed that SNHG10 expression was upregulated in EMT-exo compared with that in non-EMT-exo. Moreover, SNHG10 expression was upregulated in tumor tissues in CRC, which was associated with poor prognosis. Overexpression of SNHG10 in exosomes (oe-lnc-SNHG10 exo) significantly suppressed the viability and cytotoxicity of NK cells. Transcriptome sequencing of NK cells revealed that the expression levels of 114 genes were upregulated in the oe-lnc-SNHG10 exo group, including inhibin subunit beta C (INHBC), which was involved in the TGF-β signaling pathway. Si-INHBC treatment abrogated the effect of oe-lnc-SNHG10 exo on NK cells. oe-lnc-SNHG10 e...