Department of Radiation Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China.
Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China.
Cancer Biomark. 2024;40(2):171-184. doi: 10.3233/CBM-230337.
GINS2 exerts a carcinogenic effect in multiple human malignancies, while it is still unclear that the potential roles and underlying mechanisms of GINS2 in HNSCC.
TCGA database was used to screen out genes with significant differences in expression in HNSCC. Immunohistochemistry and qRT-PCR were used to measure the expression of GINS2 in HNSCC tissues and cells. GINS2 was detected by qRT-PCR or western blot after knockdown or overexpression. Celigo cell counting, MTT, colony formation, and flow cytometric assay were used to check the ability of proliferation and apoptosis. Bioinformatics and microarray were used to screen out the downstream genes of GINS2.
GINS2 in HNSCC tissues and cells was up-regulated, which was correlated with poor prognosis. GINS2 gene expression was successfully inhibited and overexpressed in HNSCC cells. Knockdown of GINS2 could inhibit proliferation and increase apoptosis of cells. Meanwhile, overexpression of GINS2 could enhance cell proliferation and colony formation. Knockdown of RRM2 may inhibit HNSCC cell proliferation, while overexpression of RRM2 rescued the effect of reducing GINS2 expression.
Our study reported the role of GINS2 in HNSCC for the first time. The results demonstrated that in HNSCC cells, GINS2 promoted proliferation and inhibited apoptosis via altering RRM2 expression. Therefore, GINS2 might play a carcinogen in HNSCC, and become a specific promising therapeutic target.
GINS2 在多种人类恶性肿瘤中发挥致癌作用,而 GINS2 在头颈部鳞状细胞癌(HNSCC)中的潜在作用和潜在机制尚不清楚。
使用 TCGA 数据库筛选出 HNSCC 中表达差异显著的基因。采用免疫组织化学和 qRT-PCR 检测 GINS2 在 HNSCC 组织和细胞中的表达。敲低或过表达后,通过 qRT-PCR 或 Western blot 检测 GINS2 的表达。Celigo 细胞计数、MTT、集落形成和流式细胞术检测用于检查增殖和凋亡能力。生物信息学和微阵列筛选 GINS2 的下游基因。
GINS2 在 HNSCC 组织和细胞中上调,与预后不良相关。成功抑制和过表达了 HNSCC 细胞中的 GINS2 基因表达。敲低 GINS2 可抑制细胞增殖并增加细胞凋亡。同时,过表达 GINS2 可增强细胞增殖和集落形成。敲低 RRM2 可能抑制 HNSCC 细胞增殖,而过表达 RRM2 则挽救了降低 GINS2 表达的作用。
本研究首次报道了 GINS2 在 HNSCC 中的作用。结果表明,在 HNSCC 细胞中,GINS2 通过改变 RRM2 表达促进增殖并抑制凋亡。因此,GINS2 可能在 HNSCC 中发挥致癌作用,并成为一个特定的有前途的治疗靶点。