Department of Hematology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410080, Hunan, China; Department of Medical Microbiology, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China; Key Laboratory of Cancer Carcinogenesis and Invasion of Chinese Ministry of Education, NHC Key Laboratory of Carcinogenesis, Central South University, Changsha, Hunan 410078, China; China-Africa Research Center of Infectious Diseases, Central South University, Changsha, Hunan 410078, China.
Department of Hematology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410080, Hunan, China; Key Laboratory of Cancer Carcinogenesis and Invasion of Chinese Ministry of Education, NHC Key Laboratory of Carcinogenesis, Central South University, Changsha, Hunan 410078, China; China-Africa Research Center of Infectious Diseases, Central South University, Changsha, Hunan 410078, China.
Int J Biol Macromol. 2024 Oct;278(Pt 4):134837. doi: 10.1016/j.ijbiomac.2024.134837. Epub 2024 Aug 22.
Nasopharyngeal carcinoma (NPC) is closely related to Epstein-Barr virus (EBV) infection. Long noncoding RNAs (lncRNAs) play important roles in cancers. However, the molecular mechanism underlying the roles of lncRNAs in EBV-associated NPC remains largely unclear. In this study, we confirmed that the expression of the lncRNA brain cytoplasmic 200 (BC200) was significantly increased in EBV-infected NPC cells and tissues. BC200 facilitated the growth and migration of NPC cells, suggesting that it participated in NPC progression by functioning as an oncogene. Mechanistically, BC200 was found to act as a ceRNA by sponging and inhibiting miR-6834-5p. Thymidylate synthetase (TYMS), whose high expression was reported to be an independent indicator of poor prognosis in NPC via an unknown mechanism, was identified as a target gene of miR-6834-5p in the present study. BC200 upregulated TYMS expression in a manner that depends on miR-6834-5p. TYMS was abnormally upregulated in EBV-positive NPC cells and tissues, and its ectopic expression contributed to the proliferation and migration of NPC cells. This study highlights the role of lncRNA BC200, which is upregulated by EBV, in promoting the development of NPC, suggesting that BC200-mediated ceRNA network may be valuable biomarkers for the diagnosis and treatment of EBV-associated NPC.
鼻咽癌（NPC）与 Epstein-Barr 病毒（EBV）感染密切相关。长链非编码 RNA（lncRNA）在癌症中发挥重要作用。然而，lncRNA 在 EBV 相关 NPC 中的作用的分子机制在很大程度上仍不清楚。在这项研究中，我们证实 lncRNA 脑细胞质 200（BC200）在 EBV 感染的 NPC 细胞和组织中的表达显著增加。BC200 促进 NPC 细胞的生长和迁移，表明其作为癌基因参与 NPC 进展。机制上，BC200 被发现通过海绵吸附和抑制 miR-6834-5p 发挥 ceRNA 作用。胸苷酸合成酶（TYMS）的高表达被报道通过未知机制是 NPC 预后不良的独立指标，本研究鉴定其为 miR-6834-5p 的靶基因。BC200 以依赖于 miR-6834-5p 的方式上调 TYMS 表达。EBV 阳性 NPC 细胞和组织中 TYMS 异常上调，其异位表达促进 NPC 细胞的增殖和迁移。这项研究强调了 EBV 上调的 lncRNA BC200 在促进 NPC 发展中的作用，表明 BC200 介导的 ceRNA 网络可能是 EBV 相关 NPC 的诊断和治疗有价值的生物标志物。
