Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea.
Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Chungnam National University, Daejeon 35015, Korea.
Int J Mol Sci. 2022 Aug 26;23(17):9714. doi: 10.3390/ijms23179714.
Various enzymes in the one-carbon metabolic pathway are closely related to the development of tumors, and they can all be potential targets for cancer therapy. Serine hydroxymethyltransferase2 (), a key metabolic enzyme, is very important for the proliferation and growth of cancer cells. However, the function and mechanism of in head and neck cancer (HNC) are not clear. An analysis of The Cancer Genome Atlas (TCGA) data showed that the expression of was higher in tumor tissue than in normal tissue, and its expression was significantly associated with male sex, aggressive histological grade, lymph node metastasis, distant metastasis, advanced TNM stage, and lymphovascular invasion in HNC. knockdown in FADU and SNU1041 cell lines significantly inhibited cell proliferation, colony formation, migration, and invasion. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using TCGA data revealed that was closely related to cancer stem cell regulation and maintenance. Furthermore, we found that silencing inhibited the expression of stemness markers and tumor spheroid formation compared with a control group. On the contrary, stemness markers were significantly increased after overexpression in HEP-2 cells. Interestingly, we found that knocking down reduced the expression of genes related to the Notch and Wnt pathways. Finally, silencing significantly reduced tumor growth and decreased stemness markers in a xenograft model. Taken together, our study suggests that targeting may play an important role in inhibiting HNC progression.
一碳代谢途径中的各种酶与肿瘤的发生发展密切相关，它们都可能成为癌症治疗的潜在靶点。丝氨酸羟甲基转移酶 2()是一种关键的代谢酶，对癌细胞的增殖和生长非常重要。然而，在头颈部癌症（HNC）中 的确切功能和机制尚不清楚。对癌症基因组图谱（TCGA）数据的分析表明，与正常组织相比，肿瘤组织中 的表达水平更高，其表达与男性、侵袭性组织学分级、淋巴结转移、远处转移、晚期 TNM 分期和血管淋巴管侵犯显著相关。在 FADU 和 SNU1041 细胞系中敲低 显著抑制细胞增殖、集落形成、迁移和侵袭。此外，使用 TCGA 数据进行的基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析表明，与癌症干细胞的调节和维持密切相关。此外，我们发现与对照组相比，沉默 可抑制干细胞标志物的表达和肿瘤球体形成。相反，在 HEP-2 细胞中转染 后，干细胞标志物的表达显著增加。有趣的是，我们发现敲低 可降低与 Notch 和 Wnt 通路相关的基因的表达。最后，沉默 可显著抑制异种移植模型中的肿瘤生长并降低干细胞标志物的表达。综上所述，我们的研究表明，靶向 可能在抑制 HNC 进展方面发挥重要作用。
