Diagnostic value of exosomal circMYC in radioresistant nasopharyngeal carcinoma
Yanwei Luo PhD
Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Changsha, China
Search for more papers by this authorJinqi Ma MD
Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Changsha, China
Search for more papers by this authorFengxia Liu MD
Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Changsha, China
Search for more papers by this authorCorresponding Author
Jie Guo PhD
National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha, China
Correspondence
Jie Guo, National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, Hunan, China.
Email: [email protected]
Rong Gui, Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Tongzipo Road 138, Changsha 410013, Hunan, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Rong Gui PhD
Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Changsha, China
Correspondence
Jie Guo, National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, Hunan, China.
Email: [email protected]
Rong Gui, Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Tongzipo Road 138, Changsha 410013, Hunan, China.
Email: [email protected]
Search for more papers by this authorYanwei Luo PhD
Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Changsha, China
Search for more papers by this authorJinqi Ma MD
Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Changsha, China
Search for more papers by this authorFengxia Liu MD
Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Changsha, China
Search for more papers by this authorCorresponding Author
Jie Guo PhD
National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha, China
Correspondence
Jie Guo, National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, Hunan, China.
Email: [email protected]
Rong Gui, Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Tongzipo Road 138, Changsha 410013, Hunan, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Rong Gui PhD
Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Changsha, China
Correspondence
Jie Guo, National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, Hunan, China.
Email: [email protected]
Rong Gui, Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Tongzipo Road 138, Changsha 410013, Hunan, China.
Email: [email protected]
Search for more papers by this authorFunding information: National Natural Science Foundation of China, Grant/Award Numbers: 81573091, 81802668; Natural Science Foundation of Hunan Province, Grant/Award Numbers: 2017JJ3467, 2018JJ3776
Abstract
Background
The relationship between circulating exosomal circular RNA (circRNA) and prognosis of patients with nasopharyngeal carcinoma (NPC) remain unknown. This study focused on the expression of exosomal circMYC and its relationship with the recurrence and prognosis of patients with NPC.
Methods
The circulating exosomes were obtained from 210 patients with NPC. Quantitative polymerase chain reaction, 5-ethynyl-2′-deoxyuridine (EdU) staining, colony formation, and bioinformatic analysis were performed.
Results
Circulating exosomal circMYC was significantly increased in patients with NPC and was associated with tumor size, lymph node metastasis, TNM stage, survival rate, and disease recurrence. Gain-functional and loss-functional experiments revealed that overexpression of circMYC promoted cell proliferation and reduce radiosensitivity, while knockdown of circMYC inhibited cell proliferation and enhanced radiotherapy.
Conclusion
circMYC is an oncogene in NPC cells and can enhance the radiotherapy resistance of NPC cells. Circulating exosomal circMYC can be used as a potential therapeutic target for NPC.
CONFLICT OF INTEREST
The authors declare no potential conflict of interest.
REFERENCES
- 1Chen YP, Chan A, Le QT, Blanchard P, Sun Y, Ma J. Nasopharyngeal carcinoma. Lancet. 2019; 394(10192): 64-80.
- 2Lee HM, Okuda KS, Gonzalez FE, Patel V. Current perspectives on nasopharyngeal carcinoma. Adv Exp Med Biol. 2019; 1164: 11-34.
- 3Lee A, Ng WT, Chan J, et al. Management of locally recurrent nasopharyngeal carcinoma. Cancer Treat Rev. 2019; 79:101890.
- 4Shi J, Tan SY, Lee A, et al. Restoring apoptosis dysregulation using survivin inhibitor in nasopharyngeal cancer. Head Neck. 2020; 42: 913-923. https://doi.org/10.1002/hed.26068
- 5Peng L, Liu JQ, Chen YP, Ma J. The next decade of clinical trials in locoregionally advanced nasopharyngeal carcinoma. Br J Radiol. 2019; 92(1102):20181031.
- 6Ye SB, Li ZL, Luo DH, et al. Tumor-derived exosomes promote tumor progression and T-cell dysfunction through the regulation of enriched exosomal microRNAs in human nasopharyngeal carcinoma. Oncotarget. 2014; 5(14): 5439-5452.
- 7Wan FZ, Chen KH, Sun YC, et al. Exosomes overexpressing miR-34c inhibit malignant behavior and reverse the radioresistance of nasopharyngeal carcinoma. J Transl Med. 2020; 18(1):12.
- 8Huang L, Hu C, Chao H, et al. Drug-resistant endothelial cells facilitate progression, EMT and chemoresistance in nasopharyngeal carcinoma via exosomes. Cell Signal. 2019; 63:109385.
- 9Zhou Y, Xia L, Lin J, et al. Exosomes in nasopharyngeal carcinoma. J Cancer. 2018; 9(5): 767-777.
- 10Bao L, You B, Shi S, et al. Metastasis-associated miR-23a from nasopharyngeal carcinoma-derived exosomes mediates angiogenesis by repressing a novel target gene TSGA10. Oncogene. 2018; 37(21): 2873-2889.
- 11Principe S, Hui AB, Bruce J, Sinha A, Liu FF, Kislinger T. Tumor-derived exosomes and microvesicles in head and neck cancer: implications for tumor biology and biomarker discovery. Proteomics. 2013; 13(10–11): 1608-1623.
- 12Lei F, Lei T, Huang Y, Yang M, Liao M, Huang W. Radio-susceptibility of nasopharyngeal carcinoma: Focus on Epstein-Barr virus, microRNAs, long non-coding RNAs and circular RNAs. Curr Mol Pharmacol. 2019; 13: 192-205. https://doi.org/10.2174/1874467213666191227104646
- 13Ke Z, Xie F, Zheng C, Chen D. CircHIPK3 promotes proliferation and invasion in nasopharyngeal carcinoma by abrogating miR-4288-induced ELF3 inhibition. J Cell Physiol. 2019; 234(2): 1699-1706.
- 14Chen L, Zhou H, Guan Z. CircRNA_000543 knockdown sensitizes nasopharyngeal carcinoma to irradiation by targeting miR-9/platelet-derived growth factor receptor B axis. Biochem Biophys Res Commun. 2019; 512(4): 786-792.
- 15Ruan H, Xiang Y, Ko J, et al. Comprehensive characterization of circular RNAs in ~1000 human cancer cell lines. Genome Med. 2019; 11(1): 55.
- 16Jin C, Dong D, Yang Z, Xia R, Tao S, Piao M. CircMYC regulates glycolysis and cell proliferation in melanoma. Cell Biochem Biophys. 2019; 78: 77-88. https://doi.org/10.1007/s12013-019-00895-0
- 17Qu JQ, Yi HM, Ye X, et al. MiRNA-203 reduces nasopharyngeal carcinoma radioresistance by targeting IL8/AKT signaling. Mol Cancer Ther. 2015; 14(11): 2653-2664.
- 18Luo Y, Fu Y, Huang R, et al. CircRNA_101505 sensitizes hepatocellular carcinoma cells to cisplatin by sponging miR-103 and promotes oxidored-nitro domain-containing protein 1 expression. Cell Death Discov. 2019; 5:121.
- 19Zhao M, Xu J, Zhong S, et al. Expression profiles and potential functions of circular RNAs in extracellular vesicles isolated from radioresistant glioma cells. Oncol Rep. 2019; 41(3): 1893-1900.
- 20Sticht C, De La Torre C, Parveen A, Gretz N. miRWalk: An online resource for prediction of microRNA binding sites. PLoS One. 2018; 13(10):e0206239.
- 21Fan L, Cao Q, Liu J, Zhang J, Li B. Circular RNA profiling and its potential for esophageal squamous cell cancer diagnosis and prognosis. Mol Cancer. 2019; 18(1): 16.
- 22Ni J, Bucci J, Malouf D, Knox M, Graham P, Li Y. Exosomes in cancer radioresistance. Front Oncol. 2019; 9: 869.
- 23Abramowicz A, Wojakowska A, Marczak L, et al. Ionizing radiation affects the composition of the proteome of extracellular vesicles released by head-and-neck cancer cells in vitro. J Radiat Res. 2019; 60(3): 289-297.
- 24Mutschelknaus L, Peters C, Winkler K, et al. Exosomes derived from squamous head and neck cancer promote cell survival after ionizing radiation. PLoS One. 2016; 11(3):e0152213.
- 25Dai X, Liao K, Zhuang Z, et al. AHIF promotes glioblastoma progression and radioresistance via exosomes. Int J Oncol. 2019; 54(1): 261-270.
- 26Yue X, Lan F, Xia T. Hypoxic glioma cell-secreted exosomal miR-301a activates Wnt/beta-catenin signaling and promotes radiation resistance by targeting TCEAL7. Mol Ther. 2019; 27(11): 1939-1949.
- 27Long L, Zhang X, Bai J, Li Y, Wang X, Zhou Y. Tissue-specific and exosomal miRNAs in lung cancer radiotherapy: From regulatory mechanisms to clinical implications. Cancer Manag Res. 2019; 11: 4413-4424.
- 28Zhang Z, Yu X, Zhou Z, et al. LMP1-positive extracellular vesicles promote radioresistance in nasopharyngeal carcinoma cells through P38 MAPK signaling. Cancer Med. 2019; 8(13): 6082-6094.
- 29Bufalino A, Cervigne NK, de Oliveira CE, et al. Low miR-143/miR-145 cluster levels induce activin A overexpression in oral squamous cell carcinomas, which contributes to poor prognosis. PLoS One. 2015; 10(8):e0136599.
- 30Tang D, Yang Z, Long F, et al. Long noncoding RNA MALAT1 mediates stem cell-like properties in human colorectal cancer cells by regulating miR-20b-5p/Oct4 axis. J Cell Physiol. 2019; 234(11): 20816-20828.
- 31Zhu H, Jin YM, Lyu XM, Fan LM, Wu F. Long noncoding RNA H19 regulates HIF-1alpha/AXL signaling through inhibiting miR-20b-5p in endometrial cancer. Cell Cycle. 2019; 18(19): 2454-2464.
- 32Zhu K, Hu X, Chen H, et al. Downregulation of circRNA DMNT3B contributes to diabetic retinal vascular dysfunction through targeting miR-20b-5p and BAMBI. EBioMedicine. 2019; 49: 341-353.
- 33Wang S, Jin S, Liu MD, et al. Hsa-let-7e-5p inhibits the proliferation and metastasis of head and neck squamous cell carcinoma cells by targeting chemokine receptor 7. J Cancer. 2019; 10(8): 1941-1948.
- 34Chiam K, Wang T, Watson DI, et al. Circulating serum exosomal miRNAs as potential biomarkers for esophageal adenocarcinoma. J Gastrointest Surg. 2015; 19(7): 1208-1215.
- 35Huang V, Zheng J, Qi Z, et al. Ago1 interacts with RNA polymerase II and binds to the promoters of actively transcribed genes in human cancer cells. PLoS Genet. 2013; 9(9):e1003821.
- 36Wang M, Zhang L, Liu Z, et al. AGO1 may influence the prognosis of hepatocellular carcinoma through TGF-beta pathway. Cell Death Dis. 2018; 9(3):324.
- 37Huber AL, Papp SJ, Chan AB, et al. CRY2 and FBXL3 cooperatively degrade c-MYC. Mol Cell. 2016; 64(4): 774-789.
- 38Lesicka M, Jablonska E, Wieczorek E, et al. A different methylation profile of circadian genes promoter in breast cancer patients according to clinicopathological features. Chronobiol Int. 2019; 36(8): 1103-1114.
- 39Rahman S, Kraljevic PS, Markova-Car E. Circadian (de)regulation in head and neck squamous cell carcinoma. Int J Mol Sci. 2019; 20(11): 2662-2662.
- 40Qiu M, Chen YB, Jin S, et al. Research on circadian clock genes in non-small-cell lung carcinoma. Chronobiol Int. 2019; 36(6): 739-750.