Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2021

Open Access 01-12-2021 | Colorectal Cancer | Primary research

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

Authors: Yiwen Huang, Yanbo Luo, Wentao Ou, Yuanyuan Wang, Dong Dong, Xiaowen Peng, Yuqi Luo

Published in: Cancer Cell International | Issue 1/2021

Login to get access

Abstract

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 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.
Appendix
Available only for authorised users
Literature
1.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.CrossRef
2.
Chen W, Sun K, Zheng R, Zeng H, Zhang S, Xia C, et al. Cancer incidence and mortality in China, 2014. Chin J Cancer Res. 2018;30(1):1–12.CrossRef
3.
Martini G, Ciardiello D, Vitiello PP, Napolitano S, Cardone C, Cuomo A, et al. Resistance to anti-epidermal growth factor receptor in metastatic colorectal cancer: what does still need to be addressed? Cancer Treat Rev. 2020;86:102023.CrossRef
4.
Tang S, Ning Q, Yang L, Mo Z, Tang S. Mechanisms of immune escape in the cancer immune cycle. Int Immunopharmacol. 2020;86:106700.CrossRef
5.
Chiossone L, Dumas PY, Vienne M, Vivier E. Natural killer cells and other innate lymphoid cells in cancer. Nat Rev Immunol. 2018;18(11):671–88.CrossRef
6.
Yu M, Pan H, Che N, Li L, Wang C, Wang Y, et al. Microwave ablation of primary breast cancer inhibits metastatic progression in model mice via activation of natural killer cells. Cell Mol Immunol. 2020.
7.
Zheng Y, Li Y, Tang B, Zhao Q, Wang D, Liu Y, et al. IL-6-induced CD39 expression on tumor-infiltrating NK cells predicts poor prognosis in esophageal squamous cell carcinoma. Cancer Immunol Immunother. 2020.
8.
Chan IS, Knutsdottir H, Ramakrishnan G, Padmanaban V, Warrier M, Ramirez JC, et al. Cancer cells educate natural killer cells to a metastasis-promoting cell state. J Cell Biol. 2020;219(9).
9.
Wang S, Zhang Y, Cong W, Liu J, Zhang Y, Fan H, et al. Breast cancer stem-like cells can promote metastasis by activating platelets and down-regulating antitumor activity of natural killer cells. J Trad Chinese Med Chung i tsa chih ying wen pan. 2016;36(4):530–7.
10.
Yarani R, Mirza AH, Kaur S, Pociot F. The emerging role of lncRNAs in inflammatory bowel disease. Exp Mol Med. 2018;50(12):1–14.CrossRef
11.
Zheng Y, Tian X, Wang T, Xia X, Cao F, Tian J, et al. Long noncoding RNA Pvt1 regulates the immunosuppression activity of granulocytic myeloid-derived suppressor cells in tumor-bearing mice. Mol Cancer. 2019;18(1):61.CrossRef
12.
Huang D, Chen J, Yang L, Ouyang Q, Li J, Lao L, et al. NKILA lncRNA promotes tumor immune evasion by sensitizing T cells to activation-induced cell death. Nat Immunol. 2018;19(10):1112–25.CrossRef
13.
Zhang R, Ni F, Fu B, Wu Y, Sun R, Tian Z, et al. A long noncoding RNA positively regulates CD56 in human natural killer cells. Oncotarget. 2016;7(45):72546–58.CrossRef
14.
Chen Z, Yang L, Cui Y, Zhou Y, Yin X, Guo J, et al. Cytoskeleton-centric protein transportation by exosomes transforms tumor-favorable macrophages. Oncotarget. 2016;7(41):67387–402.CrossRef
15.
Takano Y, Masuda T, Iinuma H, Yamaguchi R, Sato K, Tobo T, et al. Circulating exosomal microRNA-203 is associated with metastasis possibly via inducing tumor-associated macrophages in colorectal cancer. Oncotarget. 2017;8(45):78598–613.CrossRef
16.
Ni C, Fang QQ, Chen WZ, Jiang JX, Jiang Z, Ye J, et al. Breast cancer-derived exosomes transmit lncRNA SNHG16 to induce CD73 + gammadelta1 Treg cells. Signal Transduct Target Ther. 2020;5(1):41.CrossRef
17.
Yang C, Dou R, Wei C, Liu K, Shi D, Zhang C, et al. Tumor-derived exosomal microRNA-106b-5p activates EMT-cancer cell and M2-subtype TAM interaction to facilitate CRC metastasis. Mol Ther. 2021.
18.
Zhang PF, Gao C, Huang XY, Lu JC, Guo XJ, Shi GM, et al. Cancer cell-derived exosomal circUHRF1 induces natural killer cell exhaustion and may cause resistance to anti-PD1 therapy in hepatocellular carcinoma. Mol Cancer. 2020;19(1):110.CrossRef
19.
Vulpis E, Soriani A, Cerboni C, Santoni A, Zingoni A. Cancer exosomes as conveyors of stress-induced molecules: new players in the modulation of NK cell response. Int J Mol Sci. 2019;20(3).
20.
Xie M, Yu T, Jing X, Ma L, Fan Y, Yang F, et al. Exosomal circSHKBP1 promotes gastric cancer progression via regulating the miR-582-3p/HUR/VEGF axis and suppressing HSP90 degradation. Mol Cancer. 2020;19(1):112.CrossRef
21.
Wang L, Yang G, Zhao D, Wang J, Bai Y, Peng Q, et al. CD103-positive CSC exosome promotes EMT of clear cell renal cell carcinoma: role of remote MiR-19b-3p. Mol Cancer. 2019;18(1):86.CrossRef
22.
Saxena M, Kalathur RKR, Neutzner M, Christofori G. PyMT-1099, a versatile murine cell model for EMT in breast cancer. Sci Rep. 2018;8(1):12123.CrossRef
23.
Feng J, Song D, Jiang S, Yang X, Ding T, Zhang H, et al. Quercetin restrains TGF-beta1-induced epithelial–mesenchymal transition by inhibiting Twist1 and regulating E-cadherin expression. Biochem Biophys Res Commun. 2018;498(1):132–8.CrossRef
24.
Chen F, Wang N, Tan HY, Guo W, Zhang C, Feng Y. The functional roles of exosomes-derived long non-coding RNA in human cancer. Cancer Biol Ther. 2019;20(5):583–92.CrossRef
25.
Lan T, Yuan K, Yan X, Xu L, Liao H, Hao X, et al. LncRNA SNHG10 facilitates hepatocarcinogenesis and metastasis by modulating its homolog SCARNA13 via a positive feedback loop. Cancer Res. 2019;79(13):3220–34.CrossRef
26.
Zaiatz-Bittencourt V, Finlay DK, Gardiner CM. Canonical TGF-beta signaling pathway represses human NK cell metabolism. J Immunol. 2018;200(12):3934–41.CrossRef
27.
Du XY, Zheng BT, Pang Y, Zhang W, Liu M, Xu XL, et al. The potential mechanism of INHBC and CSF1R in diabetic nephropathy. Eur Rev Med Pharmacol Sci. 2020;24(4):1970–8.PubMed
28.
Kotsafti A, Scarpa M, Castagliuolo I, Scarpa M. Reactive oxygen species and antitumor immunity-from surveillance to evasion. Cancers (Basel). 2020;12(7).
29.
Zhou L, Tian Y, Guo F, Yu B, Li J, Xu H, et al. LincRNA-p21 knockdown reversed tumor-associated macrophages function by promoting MDM2 to antagonize* p53 activation and alleviate breast cancer development. Cancer Immunol Immunother. 2020;69(5):835–46.CrossRef
30.
Li GJ, Ding H, Miao D. Long-noncoding RNA HOTAIR inhibits immunologic rejection of mouse leukemia cells through activating the Wnt/beta-catenin signaling pathway in a mouse model of leukemia. J Cell Physiol. 2019;234(7):10386–96.CrossRef
31.
Zhang P, Gao C, Huang X, Lu J, Guo X, Shi G, et al. Cancer cell-derived exosomal circUHRF1 induces natural killer cell exhaustion and may cause resistance to anti-PD1 therapy in hepatocellular carcinoma. Mol Cancer. 2020;19(1):110.CrossRef
32.
Li S, Zhu A, Ren K, Li S, Chen L. IFNbeta-induced exosomal linc-EPHA6-1 promotes cytotoxicity of NK cells by acting as a ceRNA for hsa-miR-4485-5p to up-regulate NKp46 expression. Life Sci. 2020;257:118064.CrossRef
33.
Jiang B, Hailong S, Yuan J, Zhao H, Xia W, Zha Z, et al. Identification of oncogenic long noncoding RNA SNHG12 and DUXAP8 in human bladder cancer through a comprehensive profiling analysis. Biomed Pharmacother. 2018;108:500–7.CrossRef
34.
Kimmich T, Bruning A, Kaufl SD, Makovitzky J, Kuhn C, Jeschke U, et al. Inhibin/activin-betaC and -betaE subunits in the Ishikawa human endometrial adenocarcinoma cell line. Arch Gynecol Obstet. 2010;282(2):185–91.CrossRef
35.
Windelinckx A, De Mars G, Huygens W, Peeters M, Vincent B, Wijmenga C, et al. Comprehensive fine mapping of chr12q12-14 and follow-up replication identify activin receptor 1B (ACVR1B) as a muscle strength gene. Eur J Human Genet EJHG. 2011;19(2):208–15.CrossRef
36.
Sheng J, Chen W, Zhu HJ. The immune suppressive function of transforming growth factor-beta (TGF-beta) in human diseases. Growth Factors. 2015;33(2):92–101.CrossRef
37.
Fujii R, Jochems C, Tritsch SR, Wong HC, Schlom J, Hodge JW. An IL-15 superagonist/IL-15Ralpha fusion complex protects and rescues NK cell-cytotoxic function from TGF-beta1-mediated immunosuppression. Cancer Immunol Immunother. 2018;67(4):675–89.CrossRef
38.
Otegbeye F, Ojo E, Moreton S, Mackowski N, Lee DA, de Lima M, et al. Inhibiting TGF-beta signaling preserves the function of highly activated, in vitro expanded natural killer cells in AML and colon cancer models. PLoS One. 2018;13(1):e0191358.CrossRef
Metadata
Title
Exosomal lncRNA SNHG10 derived from colorectal cancer cells suppresses natural killer cell cytotoxicity by upregulating INHBC
Authors
Yiwen Huang
Yanbo Luo
Wentao Ou
Yuanyuan Wang
Dong Dong
Xiaowen Peng
Yuqi Luo
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2021
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-021-02221-2

Other articles of this Issue 1/2021

Cancer Cell International 1/2021 Go to the issue

Primary research

Silenced lncRNA SNHG14 restrains the biological behaviors of bladder cancer cells via regulating microRNA-211-3p/ESM1 axis

Primary research

Integrative analysis the characterization of peroxiredoxins in pan-cancer

Primary Research

Long non-coding RNA LINC01559 exerts oncogenic role via enhancing autophagy in lung adenocarcinoma

Review

The significance of exosomal RNAs in the development, diagnosis, and treatment of pancreatic cancer

Primary Research

IMUP and GPRC5A: two newly identified risk score indicators in pancreatic ductal adenocarcinoma

Primary research

Establishment and drug screening of patient-derived extrahepatic biliary tract carcinoma organoids
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits