AbstractObjective To screen the key exosomal long non-coding RNAs (lncRNAs) molecules that cause nasopharyngeal carcinoma cells to develop chemoradiotherapy resistance. MethodsIn vitro, a model of concurrent chemoradiotherapy for human nasopharyngeal carcinoma cells was constructed, and the continuous shock method of high-dose concurrent chemoradiotherapy was used to induce the establishment of chemoradiotherapy-resistant nasopharyngeal carcinoma cell lines, and its resistance formation was verified. Exosomes produced by chemoradiotherapy-resistant cell lines and respective mother cell lines for nasopharyngeal carcinoma were extracted and identified. Finally, biochip technology was used to detect the differential expression levels of exosomal lncRNAs. Results After 10 repeated treatments of concurrent chemoradiotherapy, CNE-1 CRR and CNE-2 CRR were successfully obtained. Compared with the mother cell lines, CNE-1 CRR and CNE-2 CRR had a tendency to transform from epithelial to interstitial morphology, and the number of cell clones was higher, and the values of average lethal dose (D0), quasi-threshould dose (Dq), survival fraction after 2 Gy irradiation (SF2) and cell survival rate were higher. Nasopharyngeal carcinoma cells were detected by PCR chip of exosomal lncRNAs. Compared with their respective mother cell lines, 18 lncRNAs in CNE-1 CRR exosomes were significantly up-regulated and 31 lncRNAs were significantly down-regulated, and 15 lncRNAs were significantly up-regulated and 38 lncRNAs were significantly down-regulated in CNE-2 CRR exosomes. CNE-1 CRR also had similar expression profiles to CNE-2 CRR. Conclusion There are significantly up-regulated and down-regulated lncRNAs in the exosomes of CNE-1 CRR and CNE-2 CRR.
Li Cheng,Xiong Wei,Cao Ruixue et al. Expression profiling of cell-derived exosomal lncRNAs resistant to concurrent chemoradiotherapy in nasopharyngeal carcinoma[J]. Chinese Journal of Radiation Oncology, 2023, 32(5): 445-450.
Li Cheng,Xiong Wei,Cao Ruixue et al. Expression profiling of cell-derived exosomal lncRNAs resistant to concurrent chemoradiotherapy in nasopharyngeal carcinoma[J]. Chinese Journal of Radiation Oncology, 2023, 32(5): 445-450.
[1] Lee AW, Tung SY, Chua DT, et al.Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma[J]. J Natl Cancer Inst, 2010,102(15):1188-1198. DOI: 10.1093/jnci/djq258. [2] Huang CJ, Huang MY, Shih MP, et al.Post-radiation sinusitis is associated with recurrence in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy[J]. Radiat Oncol, 2019,14(1):61. DOI: 10.1186/s13014-019-1261-9. [3] Peng F, Xu ZM, Wang J, et al.Recombinant human endostatin normalizes tumor vasculature and enhances radiation response in xenografted human nasopharyngeal carcinoma models[J]. PLoS One, 2012,7(4):e34646. DOI: 10.1371/journal.pone.0034646. [4] Chen JY, Ran YG, Hong CQ, et al.Anti-cancer effects of celecoxib on nasopharyngeal carcinoma HNE-1 cells expressing COX-2 oncoprotein[J]. Cytotechnology, 2010,62(5):431-438. DOI: 10.1007/s10616-010-9296-7. [5] Chen Z, Xu XH.Combining antiangiogenic therapy and radiation in nasopharyngeal carcinoma[J]. Saudi Med J, 2015,36(6):659-664. DOI: 10.15537/smj.2015.6.11460. [6] Galluzzi L, Senovilla L, Vitale I, et al.Molecular mechanisms of cisplatin resistance[J]. Oncogene, 2012,31(15):1869-1883. DOI: 10.1038/onc.2011.384. [7] He CJ, Zheng S, Luo Y, et al.Exosome theranostics: biology and translational medicine[J]. Theranostics, 2018,8(1):237-255. DOI: 10.7150/thno.21945. [8] Liu YW, Wen JP, Huang WG.Exosomes in nasopharyngeal carcinoma[J]. Clin Chim Acta, 2021,523:355-364. DOI: 10.1016/j.cca.2021.10.013. [9] Nie GH, Li Z, Duan HF, et al.lncRNA C22orf32-1 contributes to the tumorigenesis of nasopharyngeal carcinoma[J]. Oncol Lett, 2017,13(6):4487-4492. DOI: 10.3892/ol.2017.6021. [10] Zhong QM, Chen YF, Chen ZL.LncRNA MINCR regulates irradiation resistance in nasopharyngeal carcinoma cells via the microRNA-223/ZEB1 axis[J]. Cell Cycle, 2020,19(1):53-66. DOI: 10.1080/15384101.2019.1692176. [11] 李丹, 楚建军. 小剂量顺铂连续化疗对鼻咽癌CNE-1细胞放射敏感性影响的体外研究[J].四川医学,2012,33(11):1895-1898. DOI: 10.3969/j.issn.1004-0501.2012.11.010. Li D, Chu JJ.In vitro study about the effects of low-dose continuous cisplatin chemotherapy on the radiosensitivity in nasopharyngeal carcinoma cell line CNE-1[J]. Sichuan Medical Journal,2012,33(11):1895-1898. DOI: 10.3969/j.issn.1004-0501.2012.11.010. [12] Peng G, Cao RB, Li YH, et al.Alterations of cell cycle control proteins SHP‑1/2, p16, CDK4 and cyclin D1 in radioresistant nasopharyngeal carcinoma cells[J]. Mol Med Rep, 2014,10(4):1709-1716. DOI: 10.3892/mmr.2014.2463. [13] Louis CU, Straathof K, Bollard CM, et al.Adoptive transfer of EBV-specific T cells results in sustained clinical responses in patients with locoregional nasopharyngeal carcinoma[J]. J Immunother, 2010,33(9):983-990. DOI: 10.1097/CJI.0b013e3181f3cbf4. [14] Chen CB, Chen TJ, Huang CX, et al.Experience of weekly cisplatin concurrent with intensity-modulated radiotherapy for locally advanced nasopharyngeal carcinoma patients with resistance to neoadjuvant chemotherapy[J]. Medicine (Baltimore), 2017,96(44):e8434. DOI: 10.1097/MD.0000000000008434. [15] Kong FF, Zhou JJ, Du CR, et al.Long-term survival and late complications of intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma[J]. BMC Cancer, 2018,18(1):1139. DOI: 10.1186/s12885-018-5055-5. [16] Zhang W, Cai XR, Yu J, et al.Exosome-mediated transfer of lncRNA RP11‑838N2.4 promotes erlotinib resistance in non-small cell lung cancer[J]. Int J Oncol, 2018,53(2):527-538. DOI: 10.3892/ijo.2018.4412. [17] Lu YH, Chen L, Li LD, et al.Exosomes derived from brain metastatic breast cancer cells destroy the blood-brain barrier by carrying lncRNA GS1-600G8.5[J]. Biomed Res Int, 2020,2020:7461727. DOI: 10.1155/2020/7461727. [18] Xie LY, Hu ZY, Wang XY, et al.[Expression of long noncoding RNA MALAT1 gene in human nasopharyngeal carcinoma cell lines and its biological significance][J]. Nan Fang Yi Ke Da Xue Xue Bao, 2013,33(5):692-697. [19] Shi BY, Wang YD, Yin FF.MALAT1/miR-124/Capn4 axis regulates proliferation, invasion and EMT in nasopharyngeal carcinoma cells[J]. Cancer Biol Ther, 2017,18(10):792-800. DOI: 10.1080/15384047.2017.1373214. [20] He BY, Zeng JC, Chao W, et al.Serum long non-coding RNAs MALAT1, AFAP1-AS1 and AL359062 as diagnostic and prognostic biomarkers for nasopharyngeal carcinoma[J]. Oncotarget, 2017,8(25):41166-41177. DOI: 10.18632/oncotarget.17083. [21] Li XD, Lin Y, Yang X, et al.Long noncoding RNA H19 regulates EZH2 expression by interacting with miR-630 and promotes cell invasion in nasopharyngeal carcinoma[J]. Biochem Biophys Res Commun, 2016,473(4):913-919. DOI: 10.1016/j.bbrc.2016.03.150. [22] Zhu HY.Silencing long non-coding RNA H19 combined with paclitaxel inhibits nasopharyngeal carcinoma progression[J]. Int J Pediatr Otorhinolaryngol, 2020,138:110249. DOI: 10.1016/j.ijporl.2020.110249. [23] Wang YH, Guo Z, An L, et al.LINC-PINT impedes DNA repair and enhances radiotherapeutic response by targeting DNA-PKcs in nasopharyngeal cancer[J]. Cell Death Dis, 2021,12(5):454. DOI: 10.1038/s41419-021-03728-2. [24] Yi TW, Lv XX, Fan H, et al.LncRNA SNHG15 promotes the proliferation of nasopharyngeal carcinoma via sponging miR-141-3p to upregulate KLF9[J]. Eur Rev Med Pharmacol Sci, 2020,24(12):6744-6751. DOI: 10.26355/eurrev_202006_21662. [25] Li ZW, Cai XJ, Zou WT, et al.CDKN2B-AS1 promotes the proliferation, clone formation, and invasion of nasopharyngeal carcinoma cells by regulating miR-98-5p/E2F2 axis[J]. Am J Transl Res, 2021,13(12):13406-13422. [26] Peng JJ, Liu F, Zheng H, et al.IncRNA ZFAS1 contributes to the radioresistance of nasopharyngeal carcinoma cells by sponging hsa-miR-7-5p to upregulate ENO2[J]. Cell Cycle, 2021,20(1):126-141. DOI: 10.1080/15384101.2020.1864128. [27] Wang XQ, Jin QZ, Wang X, et al.LncRNA ZFAS1 promotes proliferation and migration and inhibits apoptosis in nasopharyngeal carcinoma via the PI3K/AKT pathway in vitro[J]. Cancer Biomark, 2019,26(2):171-182. DOI: 10.3233/CBM-182080. [28] Wang QS, Zhang WJ, Hao SJ.LncRNA CCAT1 modulates the sensitivity of paclitaxel in nasopharynx cancers cells via miR-181a/CPEB2 axis[J]. Cell Cycle, 2017,16(8):795-801. DOI: 10.1080/15384101.2017.1301334. [29] Yin XD, Gu XL, Li FJ, et al.LncRNA SNHG6 accelerates nasopharyngeal carcinoma progression via modulating miR-26a-5p/ARPP19 axis[J]. Bioorg Med Chem Lett, 2021,40:127955. DOI: 10.1016/j.bmcl.2021.127955. [30] Qian W, Ren ZT, Lu XG.Knockdown of long non-coding RNA TUG1 suppresses nasopharyngeal carcinoma progression by inhibiting epithelial-mesenchymal transition (EMT) via the promotion of miR-384[J]. Biochem Biophys Res Commun, 2019,509(1):56-63. DOI: 10.1016/j.bbrc.2018.12.011.