Emerging evidence indicates that the incidence of nasopharyngeal carcinoma (NPC) remains high in endemic regions despite changing environmental factors, suggesting that genetic traits contribute to its development. Recently, long non-coding RNA-microRNA-messenger RNA (lncRNA-miRNA-mRNA) axis has been reported to be implicated in the pathophysiological processes of malignancies. Moreover, initial bioinformatic analysis revealed a highly expressed lncRNA Forkhead box D3 antisense RNA1 (FOXD3-AS1) for mechanistic network underlying NPC in this present study. Therefore, this study aims to delineate the ability of lncRNA FOXD3-AS1 to influence the NPC progression. The relationship among lncRNA FOXD3-AS1, miR-185-3p, and FOXD3 was identified with bioinformatics prediction, dual-luciferase reporter gene assays, RNA-binding protein immunoprecipitation, and RNA pull-down assays. Furthermore, effects of lncRNA FOXD3-AS1 on malignant phenotypes in vitro, alongside tumor formation in vivo, of transfected NPC stem-like cells were examined with gain- and loss-of-function experiments. Our findings revealed that lncRNA FOXD3-AS1 and FOXD3 exhibited increased expression levels, while miR-185-3p exhibited diminished levels in NPC. The levels of lncRNA FOXD3-AS1 and FOXD3 were further correlated with tumor node metastasis stage and pathological type of patients with NPC. LncRNA FOXD3-AS1 was also confirmed to negatively regulate the miR-185-3p expression, which further targeted the downstream gene FOXD3. In addition, lncRNA FOXD3-AS1 knockdown repressed cell stemness, colony formation, viability, invasion, migration, and in vivo tumor growth, and accelerated cell apoptosis. Moreover, FOXD3 silencing or miR-185-3p overexpression reversed the effects of lncRNA FOXD3-AS1. Our findings provide evidence indicating that lncRNA FOXD3-AS1 could bind to miR-185-3p to upregulate the FOXD3 expression, thereby promoting the development of NPC.

新出现的证据表明，尽管环境因素发生变化，但在流行地区鼻咽癌 (NPC) 的发病率仍然很高，这表明遗传特征有助于其发展。最近，据报道，长的非编码 RNA-microRNA-信使 RNA (lncRNA-miRNA-mRNA) 轴与恶性肿瘤的病理生理过程有关。此外，最初的生物信息学分析揭示了本研究中 NPC 的机械网络的高表达 lncRNA Forkhead box D3 反义 RNA1 (FOXD3-AS1)。因此，本研究旨在描述 lncRNA FOXD3-AS1 影响 NPC 进展的能力。lncRNA FOXD3-AS1、miR-185-3p和FOXD3之间的关系通过生物信息学预测、双荧光素酶报告基因检测、RNA 结合蛋白免疫沉淀和 RNA 下拉检测进行鉴定。此外，lncRNA FOXD3-AS1 对转染的 NPC 干细胞样细胞的体外恶性表型以及体内肿瘤形成的影响通过功能获得和功能丧失实验进行了检测。我们的研究结果表明，lncRNA FOXD3-AS1 和FOXD3表现出增加的表达水平，而 miR-185-3p 在 NPC 中表现出降低的水平。lncRNA FOXD3-AS1和FOXD3的水平进一步与NPC患者的肿瘤淋巴结转移分期和病理类型相关。LncRNA FOXD3-AS1 也被证实负调控 miR-185-3p 表达，进一步靶向下游基因FOXD3. 此外，lncRNA FOXD3-AS1 敲低可抑制细胞干性、集落形成、活力、侵袭、迁移和体内肿瘤生长，并加速细胞凋亡。此外，FOXD3沉默或 miR-185-3p 过表达逆转了 lncRNA FOXD3-AS1 的作用。我们的研究结果提供了证据，表明 lncRNA FOXD3-AS1 可以与 miR-185-3p 结合以上调FOXD3的表达，从而促进 NPC 的发展。