Tumor cell-derived exosomal lncRNA LOC441178 inhibits the tumorigenesis of esophageal carcinoma through suppressing macrophage M2 polarization

Submitted: 30 July 2022
Accepted: 13 September 2022
Published: 14 October 2022
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Esophageal carcinoma (EC) is a highly malignant type of tumor. In a previous study, the authors found that long non-coding RNA (lncRNA) LOC441178 inhibited the tumorigenesis of EC. Moreover, exosomes derived from tumor cells containing lncRNAs were found to play a key role in the tumor environment; however, whether exosomes can affect the tumor microenvironment by carrying LOC441178 remains unclear. Thus, the present study aimed to clarify this. In order to assess the effects of exosomal LOC441178 in EC, cell invasion and migration were examined using the Transwell assay. Exosomes were identified using transmission electron microscopy, western blot analysis and nanoparticle tracking analysis. Furthermore, macrophage surface makers (CD206 and CD86) were analyzed using flow cytometry. Moreover, a subcutaneous xenograft mouse model was constructed to assess the role of TE-9 cells-derived exosomal LOC441178 in EC. The results revealed that LOC441178 overexpression notably suppressed the metastasis of EC cells. In addition, exosomes were successfully isolated from EC cells, and LOC441178 level was upregulated in exosomes derived from LOC441178-overexpressed EC cells. Exosomal LOC441178 also suppressed macrophage M2 polarization, and the polarized macrophages decreased EC cell invasion. Exosomes containing LOC441178 notably inhibited the growth of EC in mice. On the whole, the present study demonstrated that the delivery of LOC441178 by EC cell-secreted exosomes inhibited the tumorigenesis of EC by suppressing the polarization of M2 macrophages. These findings may provide a new theoretical basis for discovering new strategies against EC.

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Lee S, Choi Y, Park G, Jo S, Lee SS, Park J, et al. (18)F-FDG PET/CT parameters for predicting prognosis in esophageal cancer patients treated with concurrent chemoradiotherapy. Technol Cancer Res Treat 2021;20:15330338211024655. DOI: https://doi.org/10.1177/15330338211024655
Zhou X, Wang Z, Xu B, Ji N, Meng P, Gu L, et al. Long non-coding RNA NORAD protects against cerebral ischemia/reperfusion injury induced brain damage, cell apoptosis, oxidative stress and inflammation by regulating miR-30a-5p/YWHAG. Bioengineered 2021;12:9174-88. DOI: https://doi.org/10.1080/21655979.2021.1995115
Zhou W, Huang Z, Wu C, Lu S, Fu C, Ye P, et al. Investigation on the clinical efficacy and mechanism of compound kushen injection in treating esophageal cancer based on multi-dimensional network meta-analysis and in vitro experiment. J Ethnopharmacol 2021;279:114386. DOI: https://doi.org/10.1016/j.jep.2021.114386
Tan X, Mao L, Huang C, Yang W, Guo J, Chen Z, et al. Comprehensive analysis of lncRNA-miRNA-mRNA regulatory networks for microbiota-mediated colorectal cancer associated with immune cell infiltration. Bioengineered 2021;12:3410-25. DOI: https://doi.org/10.1080/21655979.2021.1940614
Kong Q, Li G, Yin G, Li K, Zhang D, Xu W. Long Noncoding RNA WDFY3-AS2 represses the progression of esophageal cancer through miR-18a/PTEN axis. J Oncol 2021;2021:9951010. DOI: https://doi.org/10.1155/2021/9951010
Zhang S, Zhao S, Han X, Zhang Y, Jin X, Yuan Y, et al. Lnc-C2orf63-4-1 confers VSMC homeostasis and prevents aortic dissection formation via STAT3 interaction. Front Cell Dev Biol. 2021;9:792051. DOI: https://doi.org/10.3389/fcell.2021.792051
Wang Y, Jin W, Wang J. Tanshinone IIA regulates microRNA125b/foxp3/caspase1 signaling and inhibits cell viability of nasopharyngeal carcinoma. Mol Med Rep 2021;23:371. DOI: https://doi.org/10.3892/mmr.2021.12010
Liang X, Lu J, Wu Z, Guo Y, Shen S, Liang J, et al. LINC00239 Interacts with C-Myc promoter-binding protein-1 (MBP-1) to promote expression of C-Myc in esophageal squamous cell carcinoma. Mol Cancer Res 2021;19:1465-75. DOI: https://doi.org/10.1158/1541-7786.MCR-20-1025
Hu W, Chen Z, Chen J, Cai D, Chen C, Fang T. LOC441178 overexpression inhibits the proliferation and migration of esophageal carcinoma cells via methylation of miR-182. Onco Targets Ther 2020;13:11253-63. DOI: https://doi.org/10.2147/OTT.S271711
Wei Y, Ma H, Zhou H, Yin H, Yang J, Song Y, et al. miR-424-5p shuttled by bone marrow stem cells-derived exosomes attenuates osteogenesis via regulating WIF1-mediated Wnt/beta-catenin axis. Aging (Albany NY) 2021;13:17190-201. DOI: https://doi.org/10.18632/aging.203169
Sharma R, Rajput VS, Jamal S, Grover A, Grover S. An immunoinformatics approach to design a multi-epitope vaccine against Mycobacterium tuberculosis exploiting secreted exosome proteins. Sci Rep 2021;11:13836. DOI: https://doi.org/10.1038/s41598-021-93266-w
Zhang E, Geng X, Shan S, Li P, Li S, Li W, et al. Exosomes derived from bone marrow mesenchymal stem cells reverse epithelial-mesenchymal transition potentially via attenuating Wnt/beta-catenin signaling to alleviate silica-induced pulmonary fibrosis. Toxicol Mech Methods 2021;31:1-40. DOI: https://doi.org/10.1080/15376516.2021.1950250
Gao Z, Wang Q, Ji M, Guo X, Li L, Su X. Exosomal lncRNA UCA1 modulates cervical cancer stem cell self-renewal and differentiation through microRNA-122-5p/SOX2 axis. J Transl Med 2021;19:229. DOI: https://doi.org/10.1186/s12967-021-02872-9
Tao Y, Tang Y, Yang Z, Wu F, Wang L, Yang L, et al. Exploration of serum exosomal LncRNA TBILA and AGAP2-AS1 as promising biomarkers for diagnosis of non-small cell lung cancer. Int J Biol Sci 2020;16:471-82. DOI: https://doi.org/10.7150/ijbs.39123
Xin L, Wu Y, Liu C, Zeng F, Wang JL, Wu DZ, et al. Exosome-mediated transfer of lncRNA HCG18 promotes M2 macrophage polarization in gastric cancer. Mol Immunol 2021;140:196-205. DOI: https://doi.org/10.1016/j.molimm.2021.10.011
Zhang K, Chen J, Li C, Yuan Y, Fang S, Liu W, et al. Exosome-mediated transfer of SNHG7 enhances docetaxel resistance in lung adenocarcinoma. Cancer Lett 2021;526:142-54. DOI: https://doi.org/10.1016/j.canlet.2021.10.029
Wang Y, Shang K, Zhang N, Zhao J, Cao B. Tumor-associated macrophage-derived exosomes promote the progression of gastric cancer by regulating the P38MAPK signaling pathway and the immune checkpoint PD-L1. Cancer Biother Radiopharm 2021. Online ahead of print. DOI: https://doi.org/10.1089/cbr.2021.0218
Yang L, Li J, Li S, Dang W, Xin S, Long S, et al. Extracellular vesicles regulated by viruses and antiviral strategies. Front Cell Dev Biol 2021;9:722020. DOI: https://doi.org/10.3389/fcell.2021.722020
Cui HY, Rong JS, Chen J, Guo J, Zhu JQ, Ruan M, et al. Exosomal microRNA-588 from M2 polarized macrophages contributes to cisplatin resistance of gastric cancer cells. World J Gastroenterol 2021;27:6079-92. DOI: https://doi.org/10.3748/wjg.v27.i36.6079
Al-Kindi SG, Xie R, Kirklin JK, Cowger J, Oliveira GH, Krabatsch T, et al. Outcomes of durable mechanical circulatory support in myocarditis: Analysis of the International Society for Heart and Lung Transplantation registry for mechanically assisted circulatory support registry. ASAIO J 2021;68:190-6. DOI: https://doi.org/10.1097/MAT.0000000000001430
Lin D, Zhang H, Liu R, Deng T, Ning T, Bai M, et al. iRGD-modified exosomes effectively deliver CPT1A siRNA to colon cancer cells, reversing oxaliplatin resistance by regulating fatty acid oxidation. Mol Oncol 2021;15:3430-46. DOI: https://doi.org/10.1002/1878-0261.13052
Sun Y, Lu X, Li H, Li X. Dihydroartemisinin inhibits IL-6-induced epithelial-mesenchymal transition in laryngeal squamous cell carcinoma via the miR-130b-3p/STAT3/beta-catenin signaling pathway. J Int Med Res 2021;49:3000605211009494. DOI: https://doi.org/10.1177/03000605211009494
Choi JD, Kim TJ, Jeong BC, Jeon HG, Jeon SS, Kang MY, et al. ISL1 promotes enzalutamide resistance in castration-resistant prostate cancer (CRPC) through epithelial to mesenchymal transition (EMT). Sci Rep 2021;11:21984. DOI: https://doi.org/10.1038/s41598-021-01003-0
Ruste V, Goldschmidt V, Laparra A, Messayke S, Danlos FX, Romano-Martin P, et al. The determinants of very severe immune-related adverse events associated with immune checkpoint inhibitors: A prospective study of the French REISAMIC registry. Eur J Cancer 2021;158:217-24. DOI: https://doi.org/10.1016/j.ejca.2021.08.048
Eldh M, Mints M, Hiltbrunner S, Ladjevardi S, Alamdari F, Johansson M, et al. Proteomic profiling of tissue exosomes indicates continuous release of malignant exosomes in urinary bladder cancer patients, even with pathologically undetectable tumour. Cancers (Basel) 2021;13:3242. DOI: https://doi.org/10.3390/cancers13133242
Chuang HC, Chen MH, Chen YM, Ciou YR, Hsueh CH, Tsai CY, et al. Induction of interferon-γ and tissue inflammation by overexpression of eosinophil cationic protein in T cells and exosomes. Arthritis Rheumatol 2022;74:92-104. DOI: https://doi.org/10.1002/art.41920
Bai X, Wang X, Ma G, Song J, Liu X, Wu X, et al. Improvement of PD-1 blockade efficacy and elimination of immune-related gastrointestinal adverse effect by mTOR inhibitor. Front Immunol 2021;12:793831. DOI: https://doi.org/10.3389/fimmu.2021.793831
Gu W, Gong L, Wu X, Yao X. Hypoxic TAM-derived exosomal miR-155-5p promotes RCC progression through HuR-dependent IGF1R/AKT/PI3K pathway. Cell Death Discov 2021;7:147. DOI: https://doi.org/10.1038/s41420-021-00525-w
Xun J, Du L, Gao R, Shen L, Wang D, Kang L, et al. Cancer-derived exosomal miR-138-5p modulates polarization of tumor-associated macrophages through inhibition of KDM6B. Theranostics 2021;11:6847-59. DOI: https://doi.org/10.7150/thno.51864
Yuan Y, Wang Z, Chen M, Jing Y, Shu W, Xie Z, et al. Macrophage-derived exosomal miR-31-5p promotes oral squamous cell carcinoma tumourigenesis through the large tumor suppressor 2-mediated hippo signalling pathway. J Biomed Nanotechnol 2021;17:822-37. DOI: https://doi.org/10.1166/jbn.2021.3066
Lv J, Li Q, Ma R, Wang Z, Yu Y, Liu H, et al. Long noncoding RNA FGD5-AS1 knockdown decrease viability, migration, and invasion of non-small cell lung cancer (NSCLC) cells by regulating the microRNA-944/MACC1 axis. Technol Cancer Res Treat 2021;20:1533033821990090. DOI: https://doi.org/10.1177/1533033821990090
Mi X, Xu R, Hong S, Xu T, Zhang W, Liu M. M2 Macrophage-derived exosomal lncRNA AFAP1-AS1 and MicroRNA-26a affect cell migration and metastasis in esophageal cancer. Mol Ther Nucleic Acids 2020;22:779-90. DOI: https://doi.org/10.1016/j.omtn.2020.09.035
Xu K, Tian H, Zhao S, Yuan D, Jiang L, Liu X, et al. Long noncoding RNA LOC441178 reduces the invasion and migration of squamous carcinoma cells by targeting ROCK1. Biomed Res Int 2018;2018:4357647. DOI: https://doi.org/10.1155/2018/4357647
Liu YJ, Zeng SH, Hu YD, Zhang YH, Li JP. Overexpression of NREP promotes migration and invasion in gastric cancer through facilitating epithelial-mesenchymal transition. Front Cell Dev Biol 2021;9:746194. DOI: https://doi.org/10.3389/fcell.2021.746194
Goswami KK, Bose A, Baral R. Macrophages in tumor: An inflammatory perspective. Clin Immunol 2021;232:108875. DOI: https://doi.org/10.1016/j.clim.2021.108875
Wang Y, Zhang Y. LncRNA CAIF suppresses LPS-induced inflammation and apoptosis of cardiomyocytes through regulating miR-16 demethylation. Immun Inflamm Dis 2021;9:1468-78. DOI: https://doi.org/10.1002/iid3.498
O'Brien EM, Spiller KL. Pro-inflammatory polarization primes macrophages to transition into a distinct M2-like phenotype in response to IL-4. J Leukoc Biol 2022;111:989-1000. DOI: https://doi.org/10.1002/JLB.3A0520-338R
Rao J, Qiu J, Ni M, Wang H, Wang P, Zhang L, et al. Macrophage Nrf2 deficiency promotes innate immune activation by Timp3-mediated RhoA/ROCK pathway in the ischemic liver. Hepatology 2021;75:1429-45. DOI: https://doi.org/10.1002/hep.32184
Luo S, Wang H, Bai L, Chen Y, Chen S, Gao K, et al. Activation of TMEM16A Ca(2+)-activated Cl(-) channels by ROCK1/moesin promotes breast cancer metastasis. J Adv Res 2021;33:253-64. DOI: https://doi.org/10.1016/j.jare.2021.03.005
Cao L, Jiang H, Yang J, Mao J, Wei G, Meng X, et al. LncRNA MIR31HG is induced by tocilizumab and ameliorates rheumatoid arthritis fibroblast-like synoviocyte-mediated inflammation via miR-214-PTEN-AKT signaling pathway. Aging (Albany NY) 2021;13:24071-85. DOI: https://doi.org/10.18632/aging.203644

Ethics Approval

All animal experiments were performed in accordance with the Ethics Committee of The Second Affiliated Hospital of Fujian Medical University.

How to Cite

Chen, J., Chen, Z. ., Hu, W. ., & Cai, D. . (2022). Tumor cell-derived exosomal lncRNA LOC441178 inhibits the tumorigenesis of esophageal carcinoma through suppressing macrophage M2 polarization. European Journal of Histochemistry, 66(4). https://doi.org/10.4081/ejh.2022.3510