Abstract
Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer. As a neoplastic disorder, NPC is a highly malignant squamous cell carcinoma that is derived from the nasopharyngeal epithelium. NPC is radiosensitive; radiotherapy or radiotherapy combining with chemotherapy are the main treatment strategies. However, both modalities are usually accompanied by complications and acquired resistance to radiotherapy is a significant impediment to effective NPC therapy. Therefore, there is an urgent need to discover effective radio-sensitization and radio-resistance biomarkers for NPC. Recent studies have shown that Epstein-Barr virus (EBV)-encoded products, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), which share several common signaling pathways, can function in radio-related NPC cells or tissues. Understanding these interconnected regulatory networks will reveal the details of NPC radiation sensitivity and resistance. In this review, we discuss and summarize the specific molecular mechanisms of NPC radio-sensitization and radio-resistance, focusing on EBV-encoded products, miRNAs, lncRNAs and circRNAs. This will provide a foundation for the discovery of more accurate, effective and specific markers related to NPC radiotherapy. EBVencoded products, miRNAs, lncRNAs and circRNAs have emerged as crucial molecules mediating the radio-susceptibility of NPC. This understanding will improve the clinical application of markers and inform the development of novel therapeutics for NPC.
Keywords: Nasopharyngeal carcinoma, radio-susceptibility, epstein-barr virus, long no-coding RNA, microRNA, circular RNA, regulation.
Graphical Abstract
[http://dx.doi.org/10.1159/000452572] [PMID: 27889776]
[http://dx.doi.org/10.1017/S1462399407000312] [PMID: 17477889]
[http://dx.doi.org/10.1016/j.semcancer.2011.12.011] [PMID: 22245473]
[http://dx.doi.org/10.1038/nrc2587] [PMID: 19148183]
[http://dx.doi.org/10.1016/j.radonc.2013.10.020] [PMID: 24231245]
[http://dx.doi.org/10.1038/srep15638] [PMID: 26497224]
[http://dx.doi.org/10.1016/j.ejca.2015.08.006] [PMID: 26318726]
[http://dx.doi.org/10.1159/000447879] [PMID: 27744436]
[http://dx.doi.org/10.7150/jca.33345] [PMID: 31413740]
[http://dx.doi.org/10.1097/CCO.0b013e328344f527] [PMID: 21330921]
[http://dx.doi.org/10.1002/jcb.25854] [PMID: 28004426]
[http://dx.doi.org/10.1186/s13014-019-1261-9] [PMID: 30971260]
[http://dx.doi.org/10.1016/j.semradonc.2015.05.006] [PMID: 26384276]
[http://dx.doi.org/10.1089/ars.2013.5668] [PMID: 24180216]
[http://dx.doi.org/10.1016/j.canlet.2016.01.035] [PMID: 26828014]
[http://dx.doi.org/10.1016/j.ccell.2014.10.006] [PMID: 25517747]
[http://dx.doi.org/10.1038/nrc.2016.92] [PMID: 27687982]
[http://dx.doi.org/10.1186/1750-9378-9-38] [PMID: 25473414]
[http://dx.doi.org/10.1002/path.4448] [PMID: 25251730]
[http://dx.doi.org/10.1038/nm0614-571] [PMID: 24901557]
[http://dx.doi.org/10.1158/1078-0432.CCR-0670-3] [PMID: 14871955]
[http://dx.doi.org/10.1098/rstb.2016.0270] [PMID: 28893937]
[http://dx.doi.org/10.1016/j.canlet.2008.02.019] [PMID: 18353539]
[http://dx.doi.org/10.4161/cbt.26606] [PMID: 24145206]
[http://dx.doi.org/10.18632/oncotarget.3331] [PMID: 25714020]
[http://dx.doi.org/10.1371/journal.pone.0024647] [PMID: 22096476]
[http://dx.doi.org/10.1016/j.canlet.2016.05.032] [PMID: 27255972]
[http://dx.doi.org/10.1016/j.canlet.2013.11.006] [PMID: 24262659]
[PMID: 26698246]
[http://dx.doi.org/10.1002/cam4.2506] [PMID: 31436393]
[http://dx.doi.org/10.1002/ijc.29206] [PMID: 25213622]
[http://dx.doi.org/10.18632/oncotarget.15526] [PMID: 28423621]
[http://dx.doi.org/10.1016/j.biopha.2018.08.146] [PMID: 30248542]
[http://dx.doi.org/10.1042/BSR20190415] [PMID: 31471531]
[http://dx.doi.org/10.1016/S1044-579X(03)00038-5] [PMID: 14563119]
[http://dx.doi.org/10.1016/0092-8674(93)90529-Y] [PMID: 8252621]
[http://dx.doi.org/10.1016/j.ejca.2007.04.002] [PMID: 17531469]
[http://dx.doi.org/10.1146/annurev.med.59.053006.104707] [PMID: 19630570]
[http://dx.doi.org/10.1186/1476-4598-12-123] [PMID: 24138931]
[http://dx.doi.org/10.1667/RR1910.1] [PMID: 20041757]
[http://dx.doi.org/10.1007/s13277-014-2581-x] [PMID: 25201065]
[PMID: 25859408]
[http://dx.doi.org/10.1038/onc.2010.345] [PMID: 20802511]
[http://dx.doi.org/10.4161/cbt.27823] [PMID: 24495954]
[http://dx.doi.org/10.1038/onc.2016.147] [PMID: 27157611]
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0317] [PMID: 25319395]
[http://dx.doi.org/10.1038/nsmb.1589] [PMID: 19377482]
[http://dx.doi.org/10.12659/MSM.915624] [PMID: 31034464]
[http://dx.doi.org/10.3892/mmr.2015.3622] [PMID: 25891118]
[http://dx.doi.org/10.1182/blood.V90.3.1168] [PMID: 9242549]
[http://dx.doi.org/10.1002/(SICI)1096-9896(199903)187:4<410:AID-PATH266>3.0.CO;2-F] [PMID: 10398099]
[http://dx.doi.org/10.3892/ijo.2014.2497] [PMID: 24919770]
[http://dx.doi.org/10.1016/j.ijrobp.2004.10.008] [PMID: 15667975]
[http://dx.doi.org/10.1089/cbr.2013.1596] [PMID: 25405832]
[http://dx.doi.org/10.1016/j.canlet.2012.10.033] [PMID: 23142283]
[http://dx.doi.org/10.1002/cam4.1924] [PMID: 30656832]
[http://dx.doi.org/10.3109/09553002.2015.1096028] [PMID: 26473472]
[http://dx.doi.org/10.1002/cam4.660] [PMID: 26922862]
[http://dx.doi.org/10.3892/mmr.2015.3221] [PMID: 25607713]
[http://dx.doi.org/10.1038/s41374-018-0169-6] [PMID: 30664712]
[http://dx.doi.org/10.1158/1535-7163.MCT-05-0400] [PMID: 16731750]
[http://dx.doi.org/10.3892/or.2017.5354] [PMID: 28075468]
[http://dx.doi.org/10.4161/cbt.11.8.14689] [PMID: 21311212]
[http://dx.doi.org/10.1016/j.kjms.2017.05.015] [PMID: 28865599]
[http://dx.doi.org/10.3892/or.2018.6538] [PMID: 30015969]
[PMID: 11559746]
[http://dx.doi.org/10.2174/1566524013666131203103147] [PMID: 24295494]
[http://dx.doi.org/10.1186/1471-2407-10-367] [PMID: 20618998]
[http://dx.doi.org/10.4161/cc.11.4.19228] [PMID: 22374676]
[PMID: 29115464]
[http://dx.doi.org/10.1158/1535-7163.MCT-15-0461] [PMID: 26304234]
[http://dx.doi.org/10.18632/oncotarget.5117 PMID: 26314966] [PMID: 26314966]
[http://dx.doi.org/10.1111/cas.12555] [PMID: 25297925]
[http://dx.doi.org/10.1016/j.ejca.2013.03.001] [PMID: 23583221]
[http://dx.doi.org/10.12659/MSM.895660] [PMID: 26390174]
[http://dx.doi.org/10.1016/j.bcp.2006.07.015] [PMID: 16965765]
[http://dx.doi.org/10.1186/s13046-016-0465-1] [PMID: 27919278]
[http://dx.doi.org/10.1158/1535-7163.MCT-17-0385] [PMID: 28698199]
[http://dx.doi.org/10.1371/journal.pone.0068614] [PMID: 23874688]
[http://dx.doi.org/10.4103/jcrt.JCRT_682_17] [PMID: 29516971]
[http://dx.doi.org/10.1016/j.taap.2009.07.034] [PMID: 19665035]
[http://dx.doi.org/10.18632/oncotarget.4138] [PMID: 26201446]
[http://dx.doi.org/10.12659/MSMBR.914572] [PMID: 30773530]
[http://dx.doi.org/10.1186/s13046-016-0480-2] [PMID: 28057028]
[http://dx.doi.org/10.3892/ol.2016.4438] [PMID: 27313684]
[http://dx.doi.org/10.1186/1475-2867-14-24] [PMID: 24602316]
[http://dx.doi.org/10.3892/or.2013.2376] [PMID: 23564023]
[http://dx.doi.org/10.1016/j.tcb.2017.11.008] [PMID: 29274663]
[http://dx.doi.org/10.1016/j.tig.2017.11.005] [PMID: 29249332]
[http://dx.doi.org/10.4161/rna.29731] [PMID: 25144332]
[http://dx.doi.org/10.1038/nrg.2015.10] [PMID: 26666209]
[http://dx.doi.org/10.1007/s00438-016-1179-y] [PMID: 26885843]
[PMID: 30527798]
[http://dx.doi.org/10.1053/j.gastro.2018.10.054] [PMID: 30445010]
[http://dx.doi.org/10.1016/j.celrep.2018.09.054] [PMID: 30332650]
[http://dx.doi.org/10.1038/s41556-019-0299-0] [PMID: 30936474]
[http://dx.doi.org/10.1186/s40591-015-0042-6] [PMID: 26082843]
[http://dx.doi.org/10.1159/000487451] [PMID: 29448252]
[http://dx.doi.org/10.1038/s41419-018-0265-y] [PMID: 29445147]
[http://dx.doi.org/10.1038/s41418-019-0381-y] [PMID: 31320749]
[http://dx.doi.org/10.1038/ncomms6383] [PMID: 25415230]
[http://dx.doi.org/10.1186/s12967-015-0464-6] [PMID: 25888911]
[http://dx.doi.org/10.1007/s13277-015-4773-4] [PMID: 27020592]
[http://dx.doi.org/10.1002/stem.154] [PMID: 19544473]
[http://dx.doi.org/10.1007/s13277-015-4227-z] [PMID: 26482776]
[http://dx.doi.org/10.1007/s13277-016-4808-5] [PMID: 26753962]
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0492] [PMID: 25504755]
[http://dx.doi.org/10.1016/j.bbrc.2015.10.002] [PMID: 26449463]
[http://dx.doi.org/10.18632/oncotarget.11437] [PMID: 27557514]
[http://dx.doi.org/10.1080/15384047.2017.1310348] [PMID: 28402230]
[http://dx.doi.org/10.1016/j.gene.2016.07.055] [PMID: 27461945]
[http://dx.doi.org/10.12659/MSM.905370] [PMID: 28985197]
[http://dx.doi.org/10.1002/jcp.28547] [PMID: 30993702]
[http://dx.doi.org/10.18632/oncotarget.18622] [PMID: 28978036]
[http://dx.doi.org/10.3233/CBM-161715] [PMID: 27983539]
[http://dx.doi.org/10.1038/cdd.2016.95] [PMID: 27716745]
[http://dx.doi.org/10.1177/1947601911407325] [PMID: 21779440]
[http://dx.doi.org/10.1038/nature01075] [PMID: 12374981]
[http://dx.doi.org/10.2147/OTT.S182573] [PMID: 30568463]
[http://dx.doi.org/10.3892/ijo.2013.2237] [PMID: 24379026]
[http://dx.doi.org/10.1186/s12885-016-2755-6] [PMID: 27599611]
[http://dx.doi.org/10.15761/JTS.1000158] [PMID: 27642518]
[http://dx.doi.org/10.1007/s00592-016-0943-0] [PMID: 27878383]
[http://dx.doi.org/10.1186/s12943-019-1002-6] [PMID: 30999909]
[http://dx.doi.org/10.1073/pnas.73.11.3852] [PMID: 1069269]
[http://dx.doi.org/10.1080/15476286.2015.1020271] [PMID: 25746834]
[http://dx.doi.org/10.1038/ncomms11215] [PMID: 27050392]
[http://dx.doi.org/10.1038/s41576-019-0158-7] [PMID: 31395983]
[http://dx.doi.org/10.7150/jca.30828] [PMID: 31602252]
[http://dx.doi.org/10.1186/s12967-016-0977-7] [PMID: 27465405]
[http://dx.doi.org/10.7717/peerj.5011] [PMID: 29922514]
[http://dx.doi.org/10.1111/1759-7714.13032] [PMID: 30883029]
[http://dx.doi.org/10.1002/jcp.27041] [PMID: 30070690]
[http://dx.doi.org/10.2147/CMAR.S218967] [PMID: 31695488]
[http://dx.doi.org/10.1186/s12935-019-0959-y] [PMID: 31582908]
[http://dx.doi.org/10.1016/j.yexmp.2019.104288] [PMID: 31344361]
[http://dx.doi.org/10.3892/ol.2018.9471] [PMID: 30405788]
[http://dx.doi.org/10.1016/j.bbrc.2019.03.126] [PMID: 30928094]