Department of Urology, The Sixth Affiliated Hospital of Wenzhou Medical University, The People's Hospital of Lishui, Lishui, P. R. China.
Cell Cycle. 2023 Jan;22(2):229-241. doi: 10.1080/15384101.2022.2112006. Epub 2022 Aug 18.
This study aimed to investigate the effects of scaffold matrix attachment region binding protein 1 (SMAR1) on the development of bladder cancer (BCa). SMAR1 expression in paired tumor and corresponding adjacent normal tissues from 55 BCa patients was detected by quantitative reverse transcription-polymerase chain reaction. BCa cells were transfected to regulate SMAR1 expression. BCa cells were treated with XAV-939, LiCl and 2-deoxyglucose. The effect of SMAR1 on the viability, proliferation, migration, invasion and Warburg effect of BCa cells was researched by counting kit-8, colony formation assay, Transwell and aerobic glycolysis assays. Western blot was performed to detect protein expression. BCa cell growth in vivo was recorded in nude mice. Immunohistochemical staining was performed for clinical and xenografted tumor tissue specimens. SMAR1 expression was down-regulated in BCa patients, associating with worse prognoses. SMAR1 knockdown enhanced the viability, proliferation, migration, invasion, EMT and Warburg effect of BCa cells. The opposite effect was found in the SMAR1 overexpression BCa cells. XAV-939 treatment reversed the elevation of β-catenin, c-Myc and Cyclin D1 proteins expression and Warburg effect in Bca cells post-SMAR1 knockdown. LiCl treatment abrogated the inhibition of β-catenin, c-Myc and Cyclin D1 proteins expression and Warburg effect proteins due to SMAR1 overexpression in BCa cells. SMAR1 overexpression inhibited the growth of BCa cells in vivo. SMAR1 might suppress the Wnt/β-catenin signaling pathway activity to inhibit the progression of BCa. It might be an effective treatment target for BCa.
本研究旨在探讨支架基质附着区结合蛋白 1(SMAR1)对膀胱癌(BCa)发展的影响。通过定量逆转录-聚合酶链反应检测 55 例 BCa 患者配对肿瘤和相应相邻正常组织中的 SMAR1 表达。转染 BCa 细胞以调节 SMAR1 表达。用 XAV-939、LiCl 和 2-脱氧葡萄糖处理 BCa 细胞。通过细胞计数试剂盒-8、集落形成实验、Transwell 和有氧糖酵解实验研究 SMAR1 对 BCa 细胞活力、增殖、迁移、侵袭和瓦伯格效应的影响。Western blot 检测蛋白表达。记录裸鼠体内 BCa 细胞生长情况。对临床和异种移植肿瘤组织标本进行免疫组织化学染色。SMAR1 在 BCa 患者中表达下调,与预后不良相关。SMAR1 敲低增强了 BCa 细胞的活力、增殖、迁移、侵袭、上皮间质转化和瓦伯格效应。在 SMAR1 过表达的 BCa 细胞中发现了相反的效果。XAV-939 处理逆转了 SMAR1 敲低后 Bca 细胞中β-catenin、c-Myc 和 Cyclin D1 蛋白表达和瓦伯格效应的升高。LiCl 处理消除了由于 SMAR1 过表达导致的 BCa 细胞中β-catenin、c-Myc 和 Cyclin D1 蛋白表达和瓦伯格效应蛋白的抑制作用。SMAR1 过表达抑制了 BCa 细胞在体内的生长。SMAR1 可能通过抑制 Wnt/β-catenin 信号通路活性来抑制 BCa 的进展。它可能是 BCa 的有效治疗靶点。