Department of Stomatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 6/F, East Zone, No. 111, Dade Road, Yuexiu District, Guangzhou, Guangdong 510120, China.
Department of Stomatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 6/F, East Zone, No. 111, Dade Road, Yuexiu District, Guangzhou, Guangdong 510120, China.
Arch Oral Biol. 2024 Aug;164:105979. doi: 10.1016/j.archoralbio.2024.105979. Epub 2024 Apr 22.
The study aimed to investigate the effects of verbascoside on oral squamous cell carcinoma (OSCC) cellular behaviors and underlying molecular mechanisms.
For this purpose, SCC9 and UM1 cell lines were treated with verbascoside, and their biological behaviors, including proliferation, migration, and invasion, were evaluated using cell counting kit-8, 5-Ethynyl-2'-deoxyuridine, and Transwell assays. The expression of methyltransferase-3 (METTL3), microRNA (miR)- 31-5p, and homeodomain interacting protein kinase-2 (HIPK2) were examined using quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between METTL3 and miR-31-5p was evaluated by RNA immunoprecipitation and methylated RNA immunoprecipitation, while the interaction between miR-31-5p and HIPK2 was evaluated by dual-luciferase reporter analysis.
The results indicated inhibition of OSCC cell proliferation, migration, and invasion post verbascoside treatment. Similarly, METTL3 was upregulated in OSCC cells and was inhibited post-verbascoside treatment. Overexpressing METTL3 promoted the cellular processes. Moreover, miR-31-5p was upregulated in OSCC cells, where METTL3 facilitated the processing of miR-31-5p in an N6-methyladenosine (m6A)-dependent manner. The HIPK2 served as miR-31-5p target, where overexpressing miR-31-5p or HIPK2 knockdown reversed the suppression of verbascoside-induced biological behaviors.
Verbascoside inhibited the progression of OSCC by inhibiting the METTL3-regulated miR-31-5p/HIPK2 axis. These findings suggested that verbascoside might be an effective drug for OSCC therapy.
本研究旨在探讨毛蕊花糖苷对口腔鳞状细胞癌（OSCC）细胞行为的影响及其潜在的分子机制。
为此，用毛蕊花糖苷处理 SCC9 和 UM1 细胞系，并通过细胞计数试剂盒-8、5-乙炔基-2'-脱氧尿苷和 Transwell 分析评估其增殖、迁移和侵袭等生物学行为。采用定量实时聚合酶链反应（qRT-PCR）检测甲基转移酶-3（METTL3）、微小 RNA（miR）-31-5p 和同源结构域相互作用蛋白激酶-2（HIPK2）的表达。通过 RNA 免疫沉淀和甲基化 RNA 免疫沉淀评估 METTL3 和 miR-31-5p 的相互作用，通过双荧光素酶报告分析评估 miR-31-5p 和 HIPK2 的相互作用。
结果表明，毛蕊花糖苷处理后可抑制 OSCC 细胞增殖、迁移和侵袭。同样，METTL3 在 OSCC 细胞中上调，并在毛蕊花糖苷处理后被抑制。过表达 METTL3 促进了细胞过程。此外，miR-31-5p 在 OSCC 细胞中上调，METTL3 以 N6-甲基腺苷（m6A）依赖性方式促进 miR-31-5p 的加工。HIPK2 是 miR-31-5p 的靶标，过表达 miR-31-5p 或 HIPK2 敲低逆转了毛蕊花糖苷诱导的生物学行为的抑制作用。
毛蕊花糖苷通过抑制 METTL3 调节的 miR-31-5p/HIPK2 轴抑制 OSCC 的进展。这些发现表明毛蕊花糖苷可能是治疗 OSCC 的有效药物。
