As an important component of the tumor microenvironment, cancer-associated fibroblasts (CAFs) secrete energy metabolites to supply energy for tumor progression. Abnormal regulation of long noncoding RNAs (lncRNAs) is thought to contribute to glucose metabolism, but the role of lncRNAs in glycolysis in oral CAFs has not been systematically examined. In the present study, by using RNA sequencing and bioinformatics analysis, we analyzed the lncRNA/mRNA profiles of normal fibroblasts (NFs) derived from normal tissues and CAFs derived from patients with oral squamous cell carcinoma (OSCC). LncRNA H19 was identified as a key lncRNA in oral CAFs and was synchronously upregulated in both oral cancer cell lines and CAFs. Using small interfering RNA (siRNA) strategies, we determined that lncRNA H19 knockdown affected proliferation, migration, and glycolysis in oral CAFs. We found that knockdown of lncRNA H19 by siRNA suppressed the MAPK signaling pathway, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and miR-675-5p. Furthermore, the lncRNA H19/miR-675-5p/PFKFB3 axis was involved in promoting the glycolysis pathway in oral CAFs, as demonstrated by a luciferase reporter system assay and treatment with a miRNA-specific inhibitor. Our study presents a new way to understand glucose metabolism in oral CAFs, theoretically providing a novel biomarker for OSCC molecular diagnosis and a new target for antitumor therapy.

作为肿瘤微环境的重要组成部分，与癌症相关的成纤维细胞（CAF）分泌能量代谢产物，为肿瘤的发展提供能量。长非编码RNA（lncRNA）的异常调节被认为有助于葡萄糖代谢，但是尚未对lncRNA在口服CAF中糖酵解中的作用进行系统的研究。在本研究中，通过使用RNA测序和生物信息学分析，我们分析了来自正常组织的正常成纤维细胞（NFs）和来自口腔鳞状细胞癌（OSCC）患者的CAF的lncRNA / mRNA图谱。LncRNA H19被确定为口腔CAF中的关键lncRNA，并且在口腔癌细胞系和CAF中均同步上调。使用小型干扰RNA（siRNA）策略，我们确定了lncRNA H19抑制作用会影响增殖，迁移，和口服CAF中的糖酵解。我们发现通过siRNA敲低lncRNA H19可抑制MAPK信号通路，6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶3（PFKFB3）和miR-675-5p。此外，lncRNA H19 / miR-675-5p / PFKFB3轴参与了口腔CAFs糖酵解途径的促进，如萤光素酶报告系统检测和miRNA特异性抑制剂治疗所证实。我们的研究提出了一种新的途径，以了解口服CAF中的葡萄糖代谢，从理论上为OSCC分子诊断提供了新的生物标记，为抗肿瘤治疗提供了新的靶点。lncRNA H19 / miR-675-5p / PFKFB3轴参与了口腔CAFs糖酵解途径的促进，如萤光素酶报告系统检测和miRNA特异性抑制剂治疗所证实。我们的研究提出了一种新的途径，以了解口服CAF中的葡萄糖代谢，从理论上为OSCC分子诊断提供了新的生物标记，为抗肿瘤治疗提供了新的靶点。lncRNA H19 / miR-675-5p / PFKFB3轴参与了口腔CAFs糖酵解途径的促进，如萤光素酶报告系统检测和miRNA特异性抑制剂治疗所证实。我们的研究提出了一种新的途径，以了解口服CAF中的葡萄糖代谢，从理论上为OSCC分子诊断提供了新的生物标记，为抗肿瘤治疗提供了新的靶点。