Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the nasopharyngeal epithelium, characterized by a distinct geographic distribution, with high incidence in southern China and Southeast Asia. Although radiotherapy and chemotherapy have advanced considerably, distant metastasis and resistance to chemoradiotherapy remain the leading causes of death in NPC patients. Long non-coding RNAs (lncRNAs) are RNA molecules longer than 200 nucleotides that do not encode proteins; they regulate gene expression at the epigenetic, transcriptional, and post-transcriptional levels and participate in the initiation and progression of various malignancies. In recent years, a growing body of evidence has shown that lncRNAs play pivotal regulatory roles in the malignant biological behaviors of NPC, including proliferation, migration and invasion, resistance to chemoradiotherapy, apoptosis and autophagy, and metabolic reprogramming. This review systematically summarizes the research advances on lncRNAs in NPC, covering their regulatory mechanisms, signaling pathways, value as clinical biomarkers, and prospects as therapeutic targets, and discusses the current limitations and future directions of the field, with the aim of providing a theoretical basis for the early diagnosis, prognostic evaluation, and targeted therapy of NPC.
References
[1]
Chen, Y.P., Chan, A.T.C., Le, Q.T., Blanchard, P., Sun, Y. and Ma, J. (2019) Nasopharyngeal Carcinoma. The Lancet, 394, 64-80. https://doi.org/10.1016/s0140-6736(19)30956-0
[2]
Young, L.S. and Dawson, C.W. (2014) Epstein-Barr Virus and Nasopharyngeal Carcinoma. Chinese Journal of Cancer, 33, 581-590.
Mattick, J.S. and Rinn, J.L. (2015) Discovery and Annotation of Long Noncoding RNAs. Nature Structural & Molecular Biology, 22, 5-7. https://doi.org/10.1038/nsmb.2942
[5]
Schmitt, A.M. and Chang, H.Y. (2016) Long Noncoding RNAs in Cancer Pathways. Cancer Cell, 29, 452-463. https://doi.org/10.1016/j.ccell.2016.03.010
[6]
Li, L., Gu, M., You, B., Shi, S., Shan, Y., Bao, L., et al. (2016) Long Non-Coding RNA ROR Promotes Proliferation, Migration and Chemoresistance of Nasopharyngeal Carcinoma. Cancer Science, 107, 1215-1222. https://doi.org/10.1111/cas.12989
[7]
Du, M., Huang, T., Wu, J., Gu, J., Zhang, N., Ding, K., et al. (2017) Long Non-Coding RNA N326322 Promotes the Proliferation and Invasion in Nasopharyngeal Carcinoma. Oncotarget, 9, 1843-1851. https://doi.org/10.18632/oncotarget.22828
[8]
Hao, Y., Zhao, H., Jin, X., He, P., Zhang, J., Dong, Q., et al. (2019) Long Non-Coding RNA DANCR Promotes Nasopharyngeal Carcinoma Cell Proliferation and Migration. Molecular Medicine Reports, 19, 2883-2889. https://doi.org/10.3892/mmr.2019.9906
[9]
Tian, Y., Ai, M., Liu, C., Wu, Y., Khan, M., Wang, B., et al. (2023) Upregulated Long Non-Coding RNA Lnc-MRPL39-2:1 Induces the Growth and Invasion of Nasopharyngeal Carcinoma by Binding to HuR and Stabilizing β-Catenin mRNA. International Journal of Biological Sciences, 19, 2349-2365. https://doi.org/10.7150/ijbs.79115
[10]
Liu, Y., Li, H., Zhang, J., Peng, J., Zhu, S., Zhang, R., et al. (2026) LINC00491 Promotes Nasopharyngeal Carcinoma Metastasis by Binding to Purine-Rich Element Binding Protein Alpha and Regulating Annexin-A1 to Activate the PI3K/AKT Pathway. International Journal of Biological Macromolecules, 358, Article ID: 151605. https://doi.org/10.1016/j.ijbiomac.2026.151605
[11]
Feng, H., Zhao, F., Luo, J., Xu, S., Liang, Z., Xu, W., et al. (2023) Long Non-Coding RNA HOTTIP Exerts an Oncogenic Function by Regulating HOXA13 in Nasopharyngeal Carcinoma. Molecular Biology Reports, 50, 6807-6818. https://doi.org/10.1007/s11033-023-08598-9
[12]
He, S.W., Xu, C., Li, Y.Q., Li, Y., Zhao, Y., Zhang, P., et al. (2020) AR-Induced Long Non-Coding RNA LINC01503 Facilitates Proliferation and Metastasis via the SFPQ-FOSL1 Axis in Nasopharyngeal Carcinoma. Oncogene, 39, 5616-5632. https://doi.org/10.1038/s41388-020-01388-8
[13]
Bo, H., Gong, Z., Zhang, W., Li, X., Zeng, Y., Liao, Q., et al. (2015) Upregulated Long Non-Coding RNA AFAP1-AS1 Expression Is Associated with Progression and Poor Prognosis of Nasopharyngeal Carcinoma. Oncotarget, 6, 20404-20418. https://doi.org/10.18632/oncotarget.4057
[14]
Jiang, N., Zhao, L., Zong, D., Yin, L., Wu, L., Chen, C., et al. (2021) Long Non-Coding RNA LUADT1 Promotes Nasopharyngeal Carcinoma Cell Proliferation and Invasion by Downregulating miR-1207-5p. Bioengineered, 12, 10716-10728. https://doi.org/10.1080/21655979.2021.2001952
[15]
Song, P. and Yin, S. (2016) Long Non-Coding RNA EWSAT1 Promotes Human Nasopharyngeal Carcinoma Cell Growth in Vitro by Targeting miR-326/-330-5p. Aging, 8, 2948-2960. https://doi.org/10.18632/aging.101103
[16]
Wang, D. and Jiang, H. (2023) Long Noncoding RNA Long Intergenic Non-Protein-Coding RNA 173 Contributes to Nasopharyngeal Carcinoma Progression by Regulating MicroRNA-765/Gremlin 1 Pathway. Human & Experimental Toxicology, 42, 1-14. https://doi.org/10.1177/09603271231172921
[17]
Song, P. and Yin, S.C. (2019) Long Non-Coding RNA 319 Facilitates Nasopharyngeal Carcinoma Carcinogenesis through Regulation of miR-1207-5p/KLF12 Axis. Gene, 680, 51-58. https://doi.org/10.1016/j.gene.2018.09.032
[18]
Li, Y., Liao, Z., Wang, R., Liang, Z., Lin, Z., Deng, S., et al. (2022) Long Non-Coding RNA SPRY4-IT1 Promotes Proliferation and Metastasis in Nasopharyngeal Carcinoma Cell. PeerJ, 10, e13221. https://doi.org/10.7717/peerj.13221
[19]
Liu, F., Wei, J.Z., Wei, S.S., et al. (2026) The Positive Feedback of lncRNA AN-RIL/miRNA-339-5p/ZBTB7A Suppresses Metastasis of Nasopharyngeal Carcinoma Cells via SREBP1-FASN. Cancer Science, 117, 105-117.
[20]
Tao, X., Liu, X., Zhao, X., Zhou, B., Cheng, C., Yan, W., et al. (2026) DNASE1L3 Functions as a Significant Metastatic Suppressor by Attenuating MYH9/β-Catenin/c-Jun/LncRNA-KDM4A-Induced E-Cadherin Ubiquitination Degradation in Nasopharyngeal Carcinoma. Cellular & Molecular Biology Letters, 31, Article No. 107. https://doi.org/10.1186/s11658-026-00911-1
[21]
He, Y., Jing, Y., Wei, F., Tang, Y., Yang, L., Luo, J., et al. (2018) Long Non-Coding RNA PVT1 Predicts Poor Prognosis and Induces Radioresistance by Regulating DNA Repair and Cell Apoptosis in Nasopharyngeal Carcinoma. Cell Death & Disease, 9, Article No. 235. https://doi.org/10.1038/s41419-018-0265-y
[22]
Mi, J., Wang, Y., He, S., Qin, X., Li, Z., Zhang, T., et al. (2024) LncRNA HOTAIRM1 Promotes Radioresistance in Nasopharyngeal Carcinoma by Modulating FTO Acetylation-Dependent Alternative Splicing of CD44. Neoplasia, 56, Article ID: 101034. https://doi.org/10.1016/j.neo.2024.101034
[23]
Jiang, J., Wang, D., Kang, M., Qian, Y., Zha, T. and Shao, C. (2026) Inhibition of Radiotherapy Sensitivity in Nasopharyngeal Carcinoma via the Long Non-Coding RNA RHPN1-AS1. Translational Cancer Research, 15, Article 62. https://doi.org/10.21037/tcr-2025-1-2852
[24]
Chen, K.L., Huang, S.W., Yao, J.J., He, S., Gong, S., Tan, X., et al. (2024) LncRNA DYNLRB2-AS1 Promotes Gemcitabine Resistance of Nasopharyngeal Carcinoma by Inhibiting the Ubiquitination Degradation of DHX9 Protein. Drug Resistance Updates, 76, Article ID: 101111. https://doi.org/10.1016/j.drup.2024.101111
[25]
Zhu, H. (2020) Silencing Long Non-Coding RNA H19 Combined with Paclitaxel Inhibits Nasopharyngeal Carcinoma Progression. International Journal of Pediatric Otorhinolaryngology, 138, Article ID: 110249. https://doi.org/10.1016/j.ijporl.2020.110249
[26]
Lin, L., Liu, X. and Lv, B. (2020) Long Non-Coding RNA MEG3 Promotes Autophagy and Apoptosis of Nasopharyngeal Carcinoma Cells via PTEN Up-Regulation by Binding to MicroRNA-21. Journal of Cellular and Molecular Medicine, 25, 61-72. https://doi.org/10.1111/jcmm.15759
[27]
Chak, W.P., Lung, R.W., Tong, J.H., Chan, S.Y., Lun, S.W., Tsao, S., et al. (2016) Downregulation of Long Non-Coding RNA MEG3 in Nasopharyngeal Carcinoma. Molecular Carcinogenesis, 56, 1041-1054. https://doi.org/10.1002/mc.22569
[28]
Zhang, T., Jin, Y. and Luo, X. (2022) Long Non-Coding RNA RGMB-AS1 Represses Nasopharyngeal Carcinoma Progression via Binding to Forkhead Box A1. Bioengineered, 13, 5564-5580. https://doi.org/10.1080/21655979.2022.2039495
[29]
Zhang, S., Chen, W., Yang, J., Ge, Z., Kong, Y., Yan, H., et al. (2026) LINC-AC092535.5 Regulates MICAL2 mRNA Level to Inhibit p53-Mediated Ferroptosis in Nasopharyngeal Carcinoma. Oncogene, 45, 1260-1274. https://doi.org/10.1038/s41388-026-03714-y
[30]
Zhu, W., Yang, Q., Yang, H., Qian, M., Ji, Y. and Liu, J. (2025) Interfered Long Non-Coding RNA HELLPAR or Up-Regulated MicroRNA-448 Inhibits Nasopharyngeal Carcinoma Progression via Suppression of ADAM10. Discover Oncology, 16, Article No. 849. https://doi.org/10.1007/s12672-025-02565-5
[31]
Jiang, L., Wang, C., Hu, Q., Xu, S. and Guo, Q. (2026) Role of the H19/miR-423-5p/DTX3L Axis in Enhancing the Malignant Phenotype of Nasopharyngeal Carcinoma Cells. Biological and Pharmaceutical Bulletin, 49, 547-556. https://doi.org/10.1248/bpb.b25-00698
[32]
Wang, Z.W., Cheng, Y.X., Zhu, Y.X., et al. (2020) Long Non-Coding RNA FOXD1-AS1 Promotes the Progression and Glycolysis of Nasopharyngeal Carcinoma by Sustaining FOXD1 Expression. American Journal of Cancer Research, 10, 3686-3704.
[33]
Zhang, J., Li, X., Hu, J., Cao, P., Yan, Q., Zhang, S., et al. (2020) Long Noncoding RNAs Involvement in Epstein-Barr Virus Infection and Tumorigenesis. Virology Journal, 17, Article No. 51. https://doi.org/10.1186/s12985-020-01308-y
[34]
Nie, Y., Liu, X., Qu, S., Song, E., Zou, H. and Gong, C. (2013) Long Non-Coding RNA HOTAIR Is an Independent Prognostic Marker for Nasopharyngeal Carcinoma Progression and Survival. Cancer Science, 104, 458-464. https://doi.org/10.1111/cas.12092
[35]
Yang, X., Lin, F. and Gao, F. (2020) Up-Regulated Long Non-Coding RNA ILF3-AS1 Indicates Poor Prognosis of Nasopharyngeal Carcinoma and Promoted Cell Metastasis. The International Journal of Biological Markers, 35, 61-70. https://doi.org/10.1177/1724600820955199
[36]
Yan, J. and Zhou, Q. (2023) LncRNA FOXP4-AS1 Silencing Inhibits Metastasis and Epithelial-Mesenchymal Transition in Nasopharyngeal Carcinoma via miR-136-5p/MAPK1. Anti-Cancer Drugs, 34, 1104-1111. https://doi.org/10.1097/cad.0000000000001510
[37]
Xia, Y., Xiao, X., Deng, X., Zhang, F., Zhang, X., Hu, Q., et al. (2017) Targeting Long Non-Coding RNA ASBEL with Oligonucleotide Antagonist for Breast Cancer Therapy. Biochemical and Biophysical Research Communications, 489, 386-392. https://doi.org/10.1016/j.bbrc.2017.05.136
[38]
Wang, L., Bitar, M., Lu, X., Jacquelin, S., Nair, S., Sivakumaran, H., et al. (2024) CRISPR-Cas13d Screens Identify KILR, a Breast Cancer Risk-Associated LncRNA That Regulates DNA Replication and Repair. Molecular Cancer, 23, Article No. 101. https://doi.org/10.1186/s12943-024-02021-y
[39]
Zhang, Z., Chen, J., Zhu, Z., Zhu, Z., Liao, X., Wu, J., et al. (2021) CRISPR-Cas13-Mediated Knockdown of LncRNA-GACAT3 Inhibited Cell Proliferation and Motility, and Induced Apoptosis by Increasing P21, Bax, and E-Cadherin Expression in Bladder Cancer. Frontiers in Molecular Biosciences, 7, Article 627774. https://doi.org/10.3389/fmolb.2020.627774
[40]
Wang, W., Zhou, Y., Wang, J., Zhang, S., Ozes, A., Gao, H., et al. (2024) Targeting Ovarian Cancer Stem Cells by Dual Inhibition of the Long Noncoding RNA HOTAIR and Lysine Methyltransferase EZH2. Molecular Cancer Therapeutics, 23, 1666-1679. https://doi.org/10.1158/1535-7163.mct-23-0314
[41]
Cao, W., Sun, Y., Liu, L., Yu, J., Ji, J., Wang, Y., et al. (2022) HOTAIR Mediates Cisplatin Resistance in Nasopharyngeal Carcinoma by Regulating miR-106a-5p/SOX4 Axis. Bioengineered, 13, 6567-6578. https://doi.org/10.1080/21655979.2022.2038429
[42]
Li, H., Huang, J., Yu, S. and Lou, Z. (2020) Long Non-Coding RNA DLEU1 Up-Regulates BIRC6 Expression by Competitively Sponging miR-381-3p to Promote Cisplatin Resistance in Nasopharyngeal Carcinoma. OncoTargets and Therapy, 13, 2037-2045. https://doi.org/10.2147/ott.s237456
[43]
Wang, S., You, H. and Yu, S. (2020) Long Non-Coding RNA HOXAAS2 Promotes the Expression Levels of Hypoxia-Inducible Factor-1α and Programmed Death-Ligand 1, and Regulates Nasopharyngeal Carcinoma Progression via miR-519. Oncology Letters, 20, Article No. 245. https://doi.org/10.3892/ol.2020.12107
[44]
Yu, H., Zhang, C., Li, W., Sun, X., Liu, Q. and Wang, D. (2021) Nano-Coated Si-SNHG14 Regulated PD-L1 Expression and Decreased Epithelial-Mesenchymal Transition in Nasopharyngeal Carcinoma Cells. Journal of Biomedical Nanotechnology, 17, 1993-2002. https://doi.org/10.1166/jbn.2021.3162
