Department of Urology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
J Exp Clin Cancer Res. 2023 Nov 2;42(1):290. doi: 10.1186/s13046-023-02860-5.
Invasion and metastasis are the main causes of unfavourable prognosis in patients diagnosed with bladder cancer. The efficacy of immunotherapy in bladder cancer remains suboptimal due to the presence of an immunosuppressive microenvironment. The novel protein family with sequence similarity 171B (FAM171B) has been identified, but its precise role and mechanism in bladder cancer remain unclear.
In this study, we conducted an analysis to investigate the associations between FAM171B expression and the prognosis and clinicopathological stage of bladder cancer. To this end, we utilized RNA sequencing data from the TCGA and GEO databases, as well as tumor tissue specimens obtained from our clinical centre. RNA sequencing analysis allowed us to examine the biological function of FAM171B at the transcriptional level in bladder cancer cells. Additionally, we used immunoprecipitation and mass spectrometry to identify the protein that interacts with FAM171B in bladder cancer cells. The effects of FAM171B on modulating tumor-associated macrophages (TAMs) and vimentin-mediated tumor progression, as well as the underlying mechanisms, were clarified by phalloidin staining, immunofluorescence staining, ELISA, RNA immunoprecipitation, flow cytometry and a bladder cancer graft model.
FAM171B expression exhibits strong positive correlation with poor survival outcomes and advanced clinicopathological stages in patients with bladder cancer. FAM171B significantly promoted bladder cancer growth and metastasis, accompanied by TAM accumulation in the microenvironment, in vivo and in vitro. Through studies of the molecular mechanism, we found that FAM171B contributes to tumor progression by stabilizing vimentin in the cytoplasm. Additionally, our research revealed that FAM171B enhances the splicing of CCL2 mRNA by interacting with heterogeneous nuclear ribonucleoprotein U (HNRNPU), ultimately leading to increased recruitment and M2 polarization of TAMs.
In this study, we identified FAM171B as a potent factor that promotes the progression of bladder cancer. These findings establish a solid theoretical foundation for considering FAM171B as a potential diagnostic and therapeutic biomarker for bladder cancer.
在诊断为膀胱癌的患者中，侵袭和转移是导致预后不良的主要原因。由于存在免疫抑制微环境，免疫疗法在膀胱癌中的疗效仍不尽如人意。新型蛋白质家族 171B（FAM171B）已被鉴定，但它在膀胱癌中的确切作用和机制仍不清楚。
在这项研究中，我们进行了分析，以研究 FAM171B 表达与膀胱癌的预后和临床病理分期之间的关系。为此，我们利用了 TCGA 和 GEO 数据库的 RNA 测序数据以及我们临床中心获得的肿瘤组织标本。RNA 测序分析使我们能够在膀胱癌细胞中从转录水平研究 FAM171B 的生物学功能。此外，我们使用免疫沉淀和质谱法鉴定了与膀胱癌细胞中 FAM171B 相互作用的蛋白质。通过鬼笔环肽染色、免疫荧光染色、ELISA、RNA 免疫沉淀、流式细胞术和膀胱癌移植模型，阐明了 FAM171B 调节肿瘤相关巨噬细胞（TAMs）和波形蛋白介导的肿瘤进展的作用及其潜在机制。
FAM171B 的表达与膀胱癌患者的不良生存结果和晚期临床病理分期呈强烈正相关。FAM171B 显著促进了膀胱癌的生长和转移，伴随着微环境中 TAMs 的积累，在体内和体外均如此。通过对分子机制的研究，我们发现 FAM171B 通过稳定细胞质中的波形蛋白促进肿瘤进展。此外，我们的研究还揭示了 FAM171B 通过与异质核核糖核蛋白 U（HNRNPU）相互作用增强 CCL2 mRNA 的剪接，最终导致 TAMs 的募集和 M2 极化增加。
在这项研究中，我们确定 FAM171B 是促进膀胱癌进展的一个有力因素。这些发现为将 FAM171B 作为膀胱癌潜在的诊断和治疗生物标志物提供了坚实的理论基础。
