Yang Tineng, Peng Xiaoyang, Huang Xi, Cao Peng, Chen Hualei
Department of Urology Surgery, The Second Affiliated Hospital of Hainan Medical University, Haikou City, Hainan Province, China.
Cell Biochem Biophys. 2025 Jun;83(2):1631-1643. doi: 10.1007/s12013-024-01573-6. Epub 2024 Oct 4.
Bladder cancer (BLCA) is a prevalent malignancy worldwide with a high recurrence rate. Collagen Type VI Alpha 1 (COL6A1) plays a key role in several cancer types. In this study, we aimed to explore the role of COL6A1 in BLCA. COL6A1 expression in BLCA was determined using The Cancer Genome Atlas database and real-time quantitative polymerase chain reaction (RT-qPCR). Counting Kit-8, wound-healing, and transwell assays were used to assess the effect of COL6A1 on T24 and 5637 cells. Apoptosis in BLCA cell lines was explored using western blotting and flow cytometry. Co-immunoprecipitation was performed to determine interactions between proteins. The role of COL6A1 in tumor growth in nude mice was evaluated by hematoxylin-eosin, immunohistochemical, and terminal deoxynucleotidyl transferase dUTP Nick-End Labeling. In BLCA, COL6A1 expression was downregulated. Moreover, the COL6A1 overexpression suppressed the viability, migration, and invasion, while promoting apoptosis of BLCA cell lines, with increased Caspase-3, Bax, and p53, and decreased Bcl-2. Conversely, silencing of COL6A1 promoted proliferation, migration, and invasion, while inhibiting apoptosis in BLCA cell lines. In vivo, COL6A1 inhibits tumor growth and progression. Fibrillin-1 (FBN1) was positively correlated with COL6A1 expression. COL6A1 could bind to FBN1 in BLCA cell lines. The expression of FBN1 in BLCA cell lines decreased after COL6A1 silencing, whereas COL6A1 overexpression upregulated FBN1 expression. COL6A1 was downregulated and exerted an inhibitory effect on the development of BLCA, and its expression was positively correlated with the expression of FBN1.
膀胱癌(BLCA)是一种在全球范围内普遍存在且复发率高的恶性肿瘤。VI型胶原蛋白α1(COL6A1)在多种癌症类型中发挥关键作用。在本研究中,我们旨在探讨COL6A1在膀胱癌中的作用。使用癌症基因组图谱数据库和实时定量聚合酶链反应(RT-qPCR)测定膀胱癌中COL6A1的表达。采用细胞增殖检测试剂盒-8、伤口愈合实验和Transwell实验评估COL6A1对T24和5637细胞的影响。通过蛋白质免疫印迹法和流式细胞术探究膀胱癌细胞系中的细胞凋亡情况。进行免疫共沉淀以确定蛋白质之间的相互作用。通过苏木精-伊红染色、免疫组织化学和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法评估COL6A1在裸鼠肿瘤生长中的作用。在膀胱癌中,COL6A1表达下调。此外,COL6A1过表达抑制了膀胱癌细胞系的活力、迁移和侵袭,同时促进细胞凋亡,伴随半胱天冬酶-3、Bax和p53增加,Bcl-2减少。相反,COL6A1沉默促进了膀胱癌细胞系的增殖、迁移和侵袭,同时抑制细胞凋亡。在体内,COL6A1抑制肿瘤生长和进展。原纤蛋白-1(FBN1)与COL6A1表达呈正相关。COL6A1可在膀胱癌细胞系中与FBN1结合。COL6A1沉默后,膀胱癌细胞系中FBN1的表达降低,而COL6A1过表达上调FBN1表达。COL6A被下调并对膀胱癌的发展发挥抑制作用,其表达与FBN1的表达呈正相关。