Xu Hao-Ran, Pang Zhen, Wang Qin-Zhang, Ou-Yang Song
Department of Urology, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, China.
Clinical Research Center for Urinary System Diseases of Xinjiang Production and Construction Corps, Shihezi, Xinjiang, China.
J Cancer. 2025 Jan 1;16(4):1066-1077. doi: 10.7150/jca.102201. eCollection 2025.
There is mounting evidence that S100 calcium-binding A8 (S100A8) is involved in inflammation and cancer. However, whether S100A8 promotes the proliferation, invasion and migration of bladder cancer (BC) is still not completely clear. To investigate the influence of S100A8 on the proliferation, migration and invasion of BC. Based on Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, genes related to the grading, staging, proliferation, migration and invasion of BC were screened, and S100A8 was selected as the target gene for further studies. Immunohistochemical staining were employed to examine the protein expression levels of S100A8 on adjacent tissues and BC tissues. The gene expression level of S100A8 in Pan cancer cell lines was analyzed through the Cancer Cell Line Encyclopedia (CCLE) database, and the HT-1376 cell line was selected for subsequent experiments. Overexpression recombinant lentivirus and short hairpin RNA-encoding lentivirus were used to overexpress and knock down S100A8 in HT-1376 cells via infection. The mRNA and protein expression levels of S100A8 were detected by reverse transcription-quantitative PCR and western blotting. The proliferation of BC cells was analyzed using Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays. The Wound‑healing assay and Transwell assay were used to estimate the migration and invasion of BC cells. The results demonstrated that S100A8 was highly expressed in BC based on the GEO and TCGA databases. In addition, compared with those of HT-1376 cells and the negative control group, the proliferation, migration and invasion of S100A8-overexpressing HT-1376 cells were enhanced, while those of S100A8-knockdown HT-1376 cells were reduced. Furthermore, S100A8 was differentially expressed in non-muscle invasive BC and muscle invasive BC, and in low- and high-grade BC. In this study, the bioinformatics and in vitro experiments revealed that S100A8 could promote the proliferation, invasion and migration of BC cells. Consequently, S1008A emerges as a promising diagnostic and therapeutic target for BC.
越来越多的证据表明,S100钙结合蛋白A8(S100A8)与炎症和癌症有关。然而,S100A8是否促进膀胱癌(BC)的增殖、侵袭和迁移仍不完全清楚。为了研究S100A8对BC增殖、迁移和侵袭的影响。基于基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)数据库,筛选出与BC分级、分期、增殖、迁移和侵袭相关的基因,并选择S100A8作为进一步研究的靶基因。采用免疫组织化学染色检测S100A8在癌旁组织和BC组织中的蛋白表达水平。通过癌症细胞系百科全书(CCLE)数据库分析S100A8在泛癌细胞系中的基因表达水平,并选择HT-1376细胞系进行后续实验。通过感染,使用过表达重组慢病毒和短发夹RNA编码慢病毒在HT-1376细胞中过表达和敲低S100A8。通过逆转录定量PCR和蛋白质印迹法检测S100A8的mRNA和蛋白表达水平。使用细胞计数试剂盒-8和5-乙炔基-2'-脱氧尿苷试验分析BC细胞的增殖情况。采用伤口愈合试验和Transwell试验评估BC细胞的迁移和侵袭能力。结果表明,基于GEO和TCGA数据库,S100A8在BC中高表达。此外,与HT-1376细胞和阴性对照组相比,过表达S100A8的HT-1376细胞的增殖、迁移和侵袭能力增强,而敲低S100A8的HT-1376细胞的增殖、迁移和侵袭能力降低。此外,S100A8在非肌层浸润性BC和肌层浸润性BC以及低级别和高级别BC中差异表达。在本研究中,生物信息学和体外实验表明,S100A8可促进BC细胞的增殖、侵袭和迁移。因此,S1008A有望成为BC的诊断和治疗靶点。