Chi Qiang, Wang Zhiyong, Xu Hui, Li Hongyang, Song Dianbin
Department of Urology, Affiliated Hospital of Chengde Medical University, No.36, Nanyingzi Street, Chengde, 067000, Hebei, People's Republic of China.
Biochem Genet. 2024 Jun 13. doi: 10.1007/s10528-024-10855-w.
Circular RNA (circRNA) has been reported to regulate the development of bladder cancer (BCa). However, the role of circ_0000758 in BCa progression is unknown. Circ_0000758 and miR-1236-3p expression, as well as ZEB2 mRNA expression were determined by qRT-PCR. BCa cell biological functions were determined by MTT assay, EdU assay, flow cytometry, wound healing assay and tube formation assay. Protein expression was detected by western blot analysis. RNA pull-down assay and dual-luciferase reporter assay were used to confirm RNA interaction. Xenograft mice models were constructed to assess the effect of circ_0000758 on BCa tumor growth. Circ_0000758 had increased expression in BCa tissues and cells. Circ_0000758 silencing could inhibit BCa cell growth, migration, angiogenesis in vitro, and tumor growth in vivo. Circ_0000758 served as a molecular sponge for miR-1236-3p, and miR-1236-3p inhibitor reversed circ_0000758 knockdown-mediated the inhibition effect on BCa cell progression. ZEB2 was targeted by miR-1236-3p, and its overexpression also revoked the suppressive effect of miR-1236-3p on BCa cell growth, migration, and angiogenesis. Besides, circ_0000758 knockdown also restrained BCa tumor growth. Circ_0000758 might promote BCa cell growth, migration, and angiogenesis by regulating the miR-1236-3p/ZEB2 axis.
据报道，环状RNA（circRNA）可调节膀胱癌（BCa）的发展。然而，circ_0000758在BCa进展中的作用尚不清楚。通过qRT-PCR测定circ_0000758和miR-1236-3p的表达以及ZEB2 mRNA的表达。通过MTT法、EdU法、流式细胞术、伤口愈合试验和管形成试验测定BCa细胞的生物学功能。通过蛋白质印迹分析检测蛋白质表达。采用RNA下拉试验和双荧光素酶报告试验来确认RNA相互作用。构建异种移植小鼠模型以评估circ_0000758对BCa肿瘤生长的影响。circ_0000758在BCa组织和细胞中的表达增加。circ_0000758沉默可抑制BCa细胞在体外的生长、迁移、血管生成以及在体内的肿瘤生长。circ_0000758作为miR-1236-3p的分子海绵，miR-1236-3p抑制剂可逆转circ_0000758敲低介导的对BCa细胞进展的抑制作用。ZEB2是miR-1236-3p的靶标，其过表达也可消除miR-1236-3p对BCa细胞生长、迁移和血管生成的抑制作用。此外，circ_0000758敲低也抑制了BCa肿瘤生长。circ_0000758可能通过调节miR-1236-3p/ZEB2轴促进BCa细胞的生长、迁移和血管生成。
