Involvement of Non-Coding RNAs in Chemo- and Radioresistance of Nasopharyngeal Carcinoma

Figures & data

Table 1 ncRNAs Affect the Radiosensitivity of miRNAs in NPC

ncRNAs	Expression	Targets	Functional Regulation	References
miR-451	↑	RAB14	↑Radio-sensitivity	[^Citation26]
miR-206	↑	IGF1	↑Radio-sensitivity	[^Citation27]
miR-593	↑	MDR1	↑Radio-sensitivity	[^Citation109]
miR-124	↑	PDCD6	↑Radio-sensitivity	[^Citation30]
miR- 24	↑	SP1	↑Radio-sensitivity	[^Citation110]
miR-124	↑	JAMA	↑Radio-sensitivity	[^Citation111]
miR-29-3p	↑	COL1A1 3ʹ-UTR	↑Radio-sensitivity	[^Citation31]
miR-24-3p	↑	Jab1/CSN5	↑Radio-sensitivity	[^Citation112]
miR-9-5p	↑	HK2	↑Radio-sensitivity	[^Citation113]
miR-21	↓	*	↑Radio-sensitivity	[^Citation114]
miR-483-5p	↑	DAPK1	↓Radio-sensitivity	[^Citation115]
miR- BART8-3p	↑	ATM/ATR	↓Radio-sensitivity	[^Citation116]
miR-383-5p	↑	RBM3	↑Radio-sensitivity	[^Citation117]
miR-139-5p	↑	EMT	↑Radio-sensitivity	[^Citation75]
miR-222	↑	PTEN	↓Radio-sensitivity	[^Citation118]
miR-181a	↑	RKIP	↓Radio-sensitivity	[^Citation119]
miR-193a-3p	↑	SRSF2	↓Radio-sensitivity	[^Citation32]
miR-205	↑	PTEN	↓Radio-sensitivity	[^Citation43]
miR-203	↑	IL8/AKT	↑Radio-sensitivity	[^Citation120]
miR‑182‑5p	↑	BNIP3	↓Radio-sensitivity	[^Citation34]
miR‐372	↑	p53	↑Radio-sensitivity	[^Citation121]
miR-23a	↓	IL-8/Stat3	↓Radio-sensitivity	[^Citation122]
miR‑150	↑	Glycogen synthase kinase‑3β	↓Radio-sensitivity	[^Citation33]
Lnc ANRIL	↓	miR-125a	↑Radio-sensitivity	[^Citation24]
Lnc XIST	↓	miR-29c	↑Radio-sensitivity	[^Citation123]
Lnc ANCR	↑	PTEN	↓Radio-sensitivity	[^Citation59]
Lnc MINCR	↑	miR-223/ZEB1	↓Radio-sensitivity	[^Citation60]
Lnc PTPRG‐AS1	↑	miR‐194‐3p	↓Radio-sensitivity	[^Citation124]
Lnc PVT1	↑	*	↓Radio-sensitivity	[^Citation61]
Lnc MALAT1	↓	miR-1/slug axis	↑Radio-sensitivity	[^Citation125]

Notes: ↑ Up-regulated and ↓ down-regulated ncRNAs in NPC, “*” target not specified.

Table 2 ncRNAs Involved in Resistance to Chemotherapy

miRNA	Expression	Drugs	Targets	Functional Regulation	References
miR-203	↑	Cisplatin	ZEB2	↑Chemo-sensitivity	[^Citation73]
miR-200c	↑	Cisplatin	c-Myc	↓Chemo-sensitivity	[^Citation74]
miR-BARTs	↑	Cisplatin, doxorubicin	BRCA1	↑Chemo-sensitivity	[^Citation76]
miR-21	↑	Cisplatin	PDCD4, Fas-L	↓Chemo-sensitivity	[^Citation77]
miRNA-19b	↑	Cisplatin	KRAS	↑Chemo-sensitivity	[^Citation78]
miRNA-29c	↑	Cisplatin	Mcl-1, Bcl-2	↑Chemo-sensitivity	[^Citation79]
miR-139-5p	↑	Cisplatin	EMT	↑Chemo-sensitivity	[^Citation75]
miRNA-132	↑	Cisplatin	FOXA1	↑Chemo-sensitivity	[^Citation80]
miR-34c	↓	Cisplatin	SOX4	↓Chemo-sensitivity	[^Citation126]
miR-96-5p	↑	Cisplatin	CDK1	↑Chemo-sensitivity	[^Citation127]
miR-183	↑	Cisplatin	MTA1	↑Chemo-sensitivity	[^Citation128]
miR-634	↑	Paclitaxel	*	↑Chemo-sensitivity	[^Citation129]
miR-1204	↑	Paclitaxel	*	↑Chemo-sensitivity	[^Citation130]
miR-1278	↑	Cisplatin	ATG2B	↑Chemo-sensitivity	[^Citation131]
miR-29c	↑	Paclitaxel	ITGB1	↑Chemo-sensitivity	[^Citation132]
miR-29a	↑	Paclitaxel	STAT3, Bcl-2	↑Chemo-sensitivity	[^Citation133]
miR-3188	↑	5-FU	mTOR	↑Chemo-sensitivity	[^Citation134]
Lnc CCAT1	↑	Paclitaxel	miR181a/CPEB2	↑Chemo-sensitivity	[^Citation105]
Lnc KCNQ1OT1	↑	Cisplatin	miR-454/USP47 axis	↓Chemo-sensitivity	[^Citation100]
Lnc SLC25A21-AS1	↑	Multidrug	miR-324-3p/IL-6 Axis	↓Chemo-sensitivity	[^Citation101]
Lnc TINCR	↑	Cisplatin	acetyl-CoA	↓Chemo-sensitivity	[^Citation135]
Lnc DLEU1	↑	Cisplatin	BIRC6	↓Chemo-sensitivity	[^Citation95]
Lnc HOXA11-AS	↓	Cisplatin	miR-454-3p/c-Met	↑Chemo-sensitivity	[^Citation96]
Lnc C00346	↑	Cisplatin	miR-342-5p	↓Chemo-sensitivity	[^Citation102]
Lnc MIAT	↑	Cisplatin	HMGB1	↓Chemo-sensitivity	[^Citation98]
Lnc NEAT1	↓	Cisplatin	Let-7a-5p	↑Chemo-sensitivity	[^Citation99]

Notes: ↑ Up-regulated and ↓ down-regulated ncRNAs in NPC, “*” target not specified.

Zhang T, Sun Q, Liu T, et al. MiR-451 increases radiosensitivity of nasopharyngeal carcinoma cells by targeting ras-related protein 14 (RAB14). Tumor Biol. 2014;35(12):12593–12599. doi:10.1007/s13277-014-2581-x

 PubMedGoogle Scholar

Wang T, Dong X-M, Zhang F-L, Zhang J-R. miR-206 enhances nasopharyngeal carcinoma radiosensitivity by targeting IGF1. Kaohsiung J Med Sci. 2017;33(9):427–432. doi:10.1016/j.kjms.2017.05.01528865599

 PubMed Web of Science ®Google Scholar

Fan H, Shao M, Huang S, et al. MiR-593 mediates curcumin-induced radiosensitization of nasopharyngeal carcinoma cells via MDR1. Oncol Lett. 2016;11(6):3729–3734. doi:10.3892/ol.2016.443827313684

 PubMed Web of Science ®Google Scholar

Zhang Y, Zheng L, Lin S, Liu Y, Wang Y, Gao F. MiR-124 enhances cell radiosensitivity by targeting PDCD6 in nasopharyngeal carcinoma. Int J Clin Exp Pathol. 2017;10(12):11461.31966501

 PubMed Web of Science ®Google Scholar

Kang M, Xiao J, Wang J, et al. MiR-24 enhances radiosensitivity in nasopharyngeal carcinoma by targeting SP1. Cancer Med. 2016;5(6):1163–1173. doi:10.1002/cam4.66026922862

 PubMed Web of Science ®Google Scholar

Tian Y, Tian Y, Tu Y, et al. microRNA‐124 inhibits stem‐like properties and enhances radiosensitivity in nasopharyngeal carcinoma cells via direct repression of expression of JAMA. J Cell Mol Med. 2020;24(17):9533–9544. doi:10.1111/jcmm.1517732681617

 PubMed Web of Science ®Google Scholar

Guo Y, Zhai J, Zhang J, Ni C, Zhou H. Improved radiotherapy sensitivity of nasopharyngeal carcinoma cells by miR-29-3p targeting COL1A1 3ʹ-UTR. Med Sci Monit. 2019;25:3161–3169. doi:10.12659/MSM.91562431034464

 PubMed Web of Science ®Google Scholar

Wang S, Pan Y, Zhang R, et al. Hsa-miR-24-3p increases nasopharyngeal carcinoma radiosensitivity by targeting both the 3′UTR and 5′UTR of Jab1/CSN5. Oncogene. 2016;35(47):6096–6108. doi:10.1038/onc.2016.14727157611

 PubMed Web of Science ®Google Scholar

Zhan S, Ni B. hsa-miR-9-5p down-regulates HK2 and confers radiosensitivity to nasopharyngeal carcinoma. Technol Cancer Res Treat. 2021;20:153303382199782. doi:10.1177/1533033821997822

 Web of Science ®Google Scholar

Zhu H, Zhu X, Cheng G, Zhou M, Lou W. Downregulation of microRNA-21 enhances radiosensitivity in nasopharyngeal carcinoma. Exp Ther Med. 2015;9(6):2185–2189. doi:10.3892/etm.2015.240326136957

 PubMed Web of Science ®Google Scholar

Tian Y, Yan M, Zheng J, et al. miR-483-5p decreases the radiosensitivity of nasopharyngeal carcinoma cells by targeting DAPK1. Lab Invest. 2019;99(5):602–611. doi:10.1038/s41374-018-0169-630664712

 PubMed Web of Science ®Google Scholar

Zhou X, Zheng J, Tang Y, et al. EBV encoded miRNA BART8-3p promotes radioresistance in nasopharyngeal carcinoma by regulating ATM/ATR signaling pathway. Biosci Rep. 2019;39(9):BSR20190415. doi:10.1042/BSR2019041531471531

 PubMed Web of Science ®Google Scholar

Ma R, Gao P, Yang H, et al. Inhibition of cell proliferation and radioresistance by miR-383-5p through targeting RNA binding protein motif (RBM3) in nasopharyngeal carcinoma. Ann Transl Med. 2021;9(2):123. doi:10.21037/atm-20-688133569425

 PubMed Web of Science ®Google Scholar

Shao Q, Zhang P, Ma Y, et al. MicroRNA-139-5p affects cisplatin sensitivity in human nasopharyngeal carcinoma cells by regulating the epithelial-to-mesenchymal transition. Gene. 2018;652:48–58. doi:10.1016/j.gene.2018.02.00329427737

 PubMed Web of Science ®Google Scholar

Wu W, Chen X, Yu S, Wang R, Zhao R, Du C. microRNA-222 promotes tumor growth and confers radioresistance in nasopharyngeal carcinoma by targeting PTEN. Mol Med Rep. 2017. doi:10.3892/mmr.2017.7931

 Web of Science ®Google Scholar

Huang W, Liu J, Hu S, et al. miR-181a upregulation promotes radioresistance of nasopharyngeal carcinoma by targeting RKIP. OTT. 2019;12:10873–10884. doi:10.2147/OTT.S228800

 Web of Science ®Google Scholar

Kong L, Wei Q, Hu X, Chen L, Li J. miR-193a-3p promotes radio-resistance of nasopharyngeal cancer cells by targeting SRSF2 gene and hypoxia signaling pathway. Med Sci Monit Basic Res. 2019;25:53–62. doi:10.12659/MSMBR.91457230773530

 PubMed Web of Science ®Google Scholar

Qu C, Liang Z, Huang J, et al. MiR-205 determines the radioresistance of human nasopharyngeal carcinoma by directly targeting PTEN. Cell Cycle. 2012;11(4):785–796. doi:10.4161/cc.11.4.1922822374676

 PubMed Web of Science ®Google Scholar

Qu J-Q, Yi H-M, Ye X, et al. MiRNA-203 reduces nasopharyngeal carcinoma radioresistance by targeting IL8/AKT signaling. Mol Cancer Ther. 2015;14(11):2653–2664. doi:10.1158/1535-7163.MCT-15-046126304234

 PubMed Web of Science ®Google Scholar

He W, Jin H, Liu Q, Sun Q. miR‑182‑5p contributes to radioresistance in nasopharyngeal carcinoma by regulating BNIP3 expression. Mol Med Rep. 2020;23(2):130. doi:10.3892/mmr.2020.1176933313953

 PubMed Web of Science ®Google Scholar

Wang Z, Mao J-W, Liu G-Y, et al. MicroRNA-372 enhances radiosensitivity while inhibiting cell invasion and metastasis in nasopharyngeal carcinoma through activating the PBK-dependent p53 signaling pathway. Cancer Med. 2019;8(2):712–728. doi:10.1002/cam4.192430656832

 PubMed Web of Science ®Google Scholar

Qu J-Q, Yi H-M, Ye X, et al. MiR-23a sensitizes nasopharyngeal carcinoma to irradiation by targeting IL-8/Stat3 pathway. Oncotarget. 2015;6(29):28341–28356. doi:10.18632/oncotarget.511726314966

 PubMed Web of Science ®Google Scholar

Huang Y, Tan D, Xiao J, Li Q, Zhang X, Luo Z. miR-150 contributes to the radioresistance in nasopharyngeal carcinoma cells by targeting glycogen synthase kinase-3β. J Can Res Ther. 2018;14(1):111. doi:10.4103/jcrt.JCRT_682_17

 PubMed Web of Science ®Google Scholar

Hu X, Jiang H, Jiang X. Downregulation of lncRNA ANRIL inhibits proliferation, induces apoptosis, and enhances radiosensitivity in nasopharyngeal carcinoma cells through regulating miR-125a. Cancer Biol Ther. 2017;18(5):331–338. doi:10.1080/15384047.2017.131034828402230

 PubMed Web of Science ®Google Scholar

Han Q, Li L, Liang H, Li Y, Xie J, Wang Z. Downregulation of lncRNA X inactive specific transcript (XIST) suppresses cell proliferation and enhances radiosensitivity by upregulating mir-29c in nasopharyngeal carcinoma cells. Med Sci Monitor. 2017;23:4798.

 PubMed Web of Science ®Google Scholar

Ma X, Zhou J, Liu J, et al. LncRNA ANCR promotes proliferation and radiation resistance of nasopharyngeal carcinoma by inhibiting PTEN expression. OTT. 2018;11:8399–8408. doi:10.2147/OTT.S182573

 Web of Science ®Google Scholar

Zhong Q, Chen Y, Chen Z. LncRNA MINCR regulates irradiation resistance in nasopharyngeal carcinoma cells via the microRNA-223/ZEB1 axis. Cell Cycle. 2020;19(1):53–66. doi:10.1080/15384101.2019.169217631760895

 PubMed Web of Science ®Google Scholar

Yi L, Ouyang L, Wang S, Li S, Yang X. Long noncoding RNA PTPRG‐AS1 acts as a microRNA‐194‐3p sponge to regulate radiosensitivity and metastasis of nasopharyngeal carcinoma cells via PRC1. J Cell Physiol. 2019;234(10):19088–19102. doi:10.1002/jcp.2854730993702

 PubMed Web of Science ®Google Scholar

He Y, Jing Y, Wei F, et al. Long non-coding RNA PVT1 predicts poor prognosis and induces radioresistance by regulating DNA repair and cell apoptosis in nasopharyngeal carcinoma. Cell Death Dis. 2018;9(2):235. doi:10.1038/s41419-018-0265-y29445147

 PubMed Web of Science ®Google Scholar

Jin C, Yan B, Lu Q, Lin Y, Ma L. The role of MALAT1/miR-1/slug axis on radioresistance in nasopharyngeal carcinoma. Tumor Biol. 2016;37(3):4025–4033. doi:10.1007/s13277-015-4227-z

 PubMedGoogle Scholar

Jiang Q, Zhou Y, Yang H, et al. A directly negative interaction of miR-203 and ZEB2 modulates tumor stemness and chemotherapy resistance in nasopharyngeal carcinoma. Oncotarget. 2016;7(41):67288–67301. doi:10.18632/oncotarget.1169127589832

 PubMedGoogle Scholar

Yang J, Wu S-P, Wang W-J, et al. A novel miR-200c/c-myc negative regulatory feedback loop is essential to the EMT process, CSC biology and drug sensitivity in nasopharyngeal cancer. Exp Cell Res. 2020;391(2):111817. doi:10.1016/j.yexcr.2020.11181732179097

 PubMed Web of Science ®Google Scholar

Lung RW, Tong JH, Ip L, et al. EBV–encoded miRNAs can sensitize nasopharyngeal carcinoma to chemotherapeutic drugs by targeting BRCA1. J Cell Mol Med. 2020;24(22):13523–13535. doi:10.1111/jcmm.1600733074587

 PubMed Web of Science ®Google Scholar

Yang G-D, Huang T-J, Peng L-X, et al. Epstein-Barr virus_encoded LMP1 upregulates MicroRNA-21 to promote the resistance of nasopharyngeal carcinoma cells to cisplatin-induced apoptosis by suppressing PDCD4 and Fas-L. PLoS One. 2013;8(10):e78355. doi:10.1371/journal.pone.007835524194922

 PubMed Web of Science ®Google Scholar

Zhang Y, Zhao Y, Liu L, et al. MicroRNA-19b promotes nasopharyngeal carcinoma more sensitive to cisplatin by suppressing KRAS. Technol Cancer Res Treat. 2018;17:153303381879365. doi:10.1177/1533033818793652

 Web of Science ®Google Scholar

Zhang J-X, Qian D, Wang F-W, et al. MicroRNA-29c enhances the sensitivities of human nasopharyngeal carcinoma to cisplatin-based chemotherapy and radiotherapy. Cancer Lett. 2013;329(1):91–98. doi:10.1016/j.canlet.2012.10.03323142283

 PubMed Web of Science ®Google Scholar

Li YL, Zhao YG, Chen B, Li XF. MicroRNA-132 sensitizes nasopharyngeal carcinoma cells to cisplatin through regulation of forkhead box A1 protein. Pharmazie. 2016;12:715–718. doi:10.1691/ph.2016.6764

 Web of Science ®Google Scholar

Bissey P-A, Teng M, Law JH, et al. MiR-34c downregulation leads to SOX4 overexpression and cisplatin resistance in nasopharyngeal carcinoma. BMC Cancer. 2020;20(1):597. doi:10.1186/s12885-020-07081-z32586280

 PubMed Web of Science ®Google Scholar

Luo X, He X, Liu X, Zhong L, Hu W. miR-96-5p suppresses the progression of nasopharyngeal carcinoma by targeting CDK1. OTT. 2020;13:7467–7477. doi:10.2147/OTT.S248338

 Web of Science ®Google Scholar

Wang G, Wang S, Li C. MiR-183 overexpression inhibits tumorigenesis and enhances DDP-induced cytotoxicity by targeting MTA1 in nasopharyngeal carcinoma. Tumour Biol. 2017;39(6):101042831770382. doi:10.1177/1010428317703825

 Google Scholar

Peng X, Cao P, He D, et al. MiR-634 sensitizes nasopharyngeal carcinoma cells to paclitaxel and inhibits cell growth both in vitro and in vivo. Int J Clin Exp Pathol. 2014;7(10):678425400759

 PubMed Web of Science ®Google Scholar

Peng X, Cao P, Li J, et al. MiR-1204 sensitizes nasopharyngeal carcinoma cells to paclitaxel both in vitro and in vivo. Cancer Biol Ther. 2015;16(2):261–267. doi:10.1080/15384047.2014.100128725756509

 PubMed Web of Science ®Google Scholar

Zhao Y, Wang P, Wu Q. miR-1278 sensitizes nasopharyngeal carcinoma cells to cisplatin and suppresses autophagy via targeting ATG2B. Mol Cell Probes. 2020;53:101597. doi:10.1016/j.mcp.2020.10159732407879

 PubMed Web of Science ®Google Scholar

Huang L, Hu C, Chao H, et al. miR-29c regulates resistance to paclitaxel in nasopharyngeal cancer by targeting ITGB1. Exp Cell Res. 2019;378(1):1–10. doi:10.1016/j.yexcr.2019.02.01230779921

 PubMed Web of Science ®Google Scholar

Gao J, Shao Z, Yan M, Fu T, Zhang L, Yan Y. Targeted regulationof STAT3 by miR-29a in mediating Taxol resistance of nasopharyngeal carcinoma cell line CNE-1. CBM. 2018;22(4):641–648. doi:10.3233/CBM-170964

 Web of Science ®Google Scholar

Zhao M, Luo R, Liu Y, et al. Author Correction: miR-3188 regulates nasopharyngeal carcinoma proliferation and chemosensitivity through a FOXO1-modulated positive feedback loop with mTOR–p-PI3K/AKT-c-JUN. Nat Commun. 2021;12(1):2997. doi:10.1038/s41467-021-22959-733990567

 PubMed Web of Science ®Google Scholar

Wang Q, Zhang W, Hao S. LncRNA CCAT1 modulates the sensitivity of paclitaxel in nasopharynx cancers cells via miR-181a/CPEB2 axis. Cell Cycle. 2017;16(8):795–801. doi:10.1080/15384101.2017.130133428358263

 PubMed Web of Science ®Google Scholar

Yuan F, Lou Z, Zhou Z, Yan X. Long non‑coding RNA KCNQ1OT1 promotes nasopharyngeal carcinoma cell cisplatin resistance via the miR‑454/USP47 axis. Int J Mol Med. 2021;47(4):54. doi:10.3892/ijmm.2021.488733576460

 PubMed Web of Science ®Google Scholar

Wang X, Wang C, Xu H, Xie H. Long non-coding RNA SLC25A21-AS1 promotes multidrug resistance in nasopharyngeal carcinoma by regulating miR-324-3p/IL-6 axis. CMAR. 2020;12:3949–3957. doi:10.2147/CMAR.S251820

 Web of Science ®Google Scholar

Zheng Z-Q, Li Z-X, Guan J-L, et al. Long noncoding RNA TINCR-mediated regulation of acetyl-CoA metabolism promotes nasopharyngeal carcinoma progression and chemoresistance. Cancer Res. 2020;80(23):5174–5188. doi:10.1158/0008-5472.CAN-19-362633067266

 PubMed Web of Science ®Google Scholar

Li H, Huang J, Yu S, Lou Z. Long non-coding RNA DLEU1 up-regulates BIRC6 expression by competitively sponging miR-381-3p to promote cisplatin resistance in nasopharyngeal carcinoma. OTT. 2020;13:2037–2045. doi:10.2147/OTT.S237456

 Web of Science ®Google Scholar

Lin F-J, Lin X-D, Xu L-Y, Zhu S-Q. Long noncoding RNA HOXA11-AS modulates the resistance of nasopharyngeal carcinoma cells to cisplatin via miR-454-3p/c-Met. Mol Cells. 2020;43:856.33115978

 PubMed Web of Science ®Google Scholar

Cui Z, Pu T, Zhang Y, Wang J, Zhao Y. Long non-coding RNA LINC00346 contributes to cisplatin resistance in nasopharyngeal carcinoma by repressing miR-342-5p. Open Biol. 2020;10(5):190286. doi:10.1098/rsob.19028632397872

 PubMed Web of Science ®Google Scholar

Zhu X, Liu L, Wang Y, et al. lncRNA MIAT/HMGB1 axis is involved in cisplatin resistance via regulating IL6-mediated activation of the JAK2/STAT3 pathway in nasopharyngeal carcinoma. Front Oncol. 2021;11:651693. doi:10.3389/fonc.2021.65169334094941

 PubMed Web of Science ®Google Scholar

Liu F, Tai Y, Ma J. LncRNA NEAT1/let-7a-5p axis regulates the cisplatin resistance in nasopharyngeal carcinoma by targeting Rsf-1 and modulating the Ras-MAPK pathway. Cancer Biol Ther. 2018;19(6):534–542. doi:10.1080/15384047.2018.145011929565706

 PubMed Web of Science ®Google Scholar