Zuo Sipeng, Wang Huixue, Li Lin, Pan Hui, Lu Linna
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China.
Front Oncol. 2022 Mar 3;12:802807. doi: 10.3389/fonc.2022.802807. eCollection 2022.
Thymidine kinase 1 (TK1) is a cell cycle-dependent kinase that catalyzes the addition of a gamma-phosphate group to thymidine. The protumorigenic role of TK1 has been reported in various malignancies. However, the role of TK1 in skin cutaneous melanoma (SKCM) remains unclear. This study aimed to explore the molecular function of TK1 in SKCM progression.
Bioinformatics data were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Subcutaneous xenografts were established to observe the effect of TK1 knockdown on the proliferation of SKCM cells . RNA sequencing (RNA-seq; deposited in Sequence Read Archive, SRX10950283-SRX10950285 for A375 control cells and SRX10950286-SRX10950288 for TK1-silenced A375 cells) and immunoprecipitation-mass spectrometry (IP-MS) were used to analyze TK1-related genes and pathways. Seahorse XF Cell Mito tests and glycolysis stress assays were conducted for metabolic testing.
TK1 was upregulated in malignant SKCM compared to that in normal tissues and cell lines. Elevated expression of TK1 was associated with poor prognosis. and assays demonstrated that TK1 promoted the proliferation and migration of SKCM cells. Moreover, TK1 was strongly associated with multiple intracellular metabolic pathways, facilitating cell mitochondrial respiration and glycolysis in SKCM malignant progression.
TK1 drives SKCM malignant progression and supports metabolic reprogramming, indicating that TK1 serves as a therapeutic target for SKCM.
胸苷激酶1（TK1）是一种细胞周期依赖性激酶，可催化将γ-磷酸基团添加到胸苷上。TK1在各种恶性肿瘤中的促肿瘤作用已有报道。然而，TK1在皮肤黑色素瘤（SKCM）中的作用仍不清楚。本研究旨在探讨TK1在SKCM进展中的分子功能。
从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）获取生物信息学数据。建立皮下异种移植模型以观察TK1敲低对SKCM细胞增殖的影响。采用RNA测序（RNA-seq；A375对照细胞的数据存于序列读取存档库，编号为SRX10950283 - SRX10950285，TK1沉默的A375细胞的数据存于序列读取存档库，编号为SRX10950286 - SRX10950288）和免疫沉淀-质谱分析（IP-MS）来分析与TK1相关的基因和信号通路。进行海马XF细胞线粒体检测和糖酵解应激试验以进行代谢测试。
与正常组织和细胞系相比，恶性SKCM中TK1表达上调。TK1表达升高与预后不良相关。 试验和 试验表明，TK1促进SKCM细胞的增殖和迁移。此外，TK1与多种细胞内代谢途径密切相关，在SKCM恶性进展过程中促进细胞线粒体呼吸和糖酵解。
TK1驱动SKCM恶性进展并支持代谢重编程，表明TK1可作为SKCM的治疗靶点。
