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

被引：77

作者：

Huang, Yiwen ^{[1
]}

Luo, Yanbo ^{[2
]}

Ou, Wentao ^{[3
]}

Wang, Yuanyuan ^{[4
]}

Dong, Dong ^{[3
]}

Peng, Xiaowen ^{[5
]}

Luo, Yuqi ^{[2
]}

机构：

[1] Southern China Univ Technol, Nansha Hosp, Guangzhou Peoples Hosp 1, Dept Emergency,Sch Med, Guangzhou, Guangdong, Peoples R China

[2] Shenzhen Longhua Dist Cent Hosp, Dept Gastrointestinal & Hepatobiliary Surg, 187 Guanlan Rd, Shenzhen 518110, Guangdong, Peoples R China

[3] Southern China Univ Technol, Nansha Hosp, Guangzhou Peoples Hosp 1, Dept Gen Surg,Sch Med, Guangzhou, Guangdong, Peoples R China

[4] Southern China Univ Technol, Nansha Hosp, Guangzhou Peoples Hosp 1, Dept Neurol,Sch Med, Guangzhou, Guangdong, Peoples R China

[5] Southern China Univ Technol, Guangzhou Peoples Hosp 1, Nansha Hosp, Dept Lab Med,Sch Med, Guangzhou, Guangdong, Peoples R China

来源：

CANCER CELL INTERNATIONAL | 2021年 / 21卷 / 01期

关键词：

Colorectal cancer; Exosomal lncRNA; Epithelial-mesenchymal transition; Immune escape; Natural killer cells; LONG NONCODING RNA;

D O I：

10.1186/s12935-021-02221-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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-beta), 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-gamma 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-beta signaling pathway. Si-INHBC treatment abrogated the effect of oe-lnc-SNHG10 exo on NK cells. oe-lnc-SNHG10 exo induced tumor growth and upregulated INHBC expression in mice and downregulated the expression of perforin, granzyme B, and NK1.1 in tumor tissues. Conclusions The CRC cell-derived exosomal lncRNA SNHG10 suppresses the function of NK cells by upregulating INHBC expression. This study provides evidence that exosomal lncRNAs contribute to immune escape by inducing NK cell inhibition and proposes a potential treatment strategy for CRC.

引用

页数：16

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