Yang Ming, Qiu Yiwen, Yang Yi, Wang Wentao
Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China.
Front Cell Dev Biol. 2022 Feb 17;10:840010. doi: 10.3389/fcell.2022.840010. eCollection 2022.
Targeting the mRNA splicing process has been identified as a therapeutic strategy for human cancer. PRPF19 is an RNA binding protein that is involved in pre-mRNA processing and repairing DNA damage; the aberrant expression of PRPF19 is potentially associated with carcinogenesis. However, the biological role of PRPF19 in hepatocellular carcinoma (HCC) is still elusive. Data obtained from TCGA, Oncomine, and GEO were used to investigate the PRPF19 expression level and its role in tumor immune infiltration, prognosis, and the tumor progression of cohorts from HCC. Using various databases and tools (UALCAN, TIMER, TISMO, and PathCards), we presented the potential mechanisms of PFPF19 upregulation, PRPF19-related pathways, and its biological functions in liver cancer. For HCC, PRPF19 expression was found upregulated both in single tumor cells and tissues. Furthermore, the increased expression of PRPF19 was significantly correlated to clinical characteristics: advanced stage, vascular invasion, high AFP, and poor prognosis of HCC. According to the tumor-immunological analysis, we found that PRPF19 is positively correlated with infiltrating myeloid-derived suppressor cells (MDSCs). Moreover, the microenvironment of HCC tissues with high expression of PRPF19 is highly immunosuppressive (lower T-lymphocytes, multiple immune checkpoints upregulated). Patients with high expression of PRPF19 and high MDSCs had a worse survival prognosis as well. TP53 mutation may have a positive effect on PRPF19 expression decreased promoter methylation of PRPF19. By TF-mRNA network analysis, key transcription factors (TFs) in TC-NER and PCS pathways (PRPF19 involved) were identified. This work implied that PRPF19 is associated with tumor immune evasion and progression, and serves as a prognostic marker for worse clinical outcomes with HCC. Thus, this critical regulator could serve as a potential therapeutic target of HCC.
靶向mRNA剪接过程已被确定为治疗人类癌症的一种策略。PRPF19是一种RNA结合蛋白，参与前体mRNA加工和DNA损伤修复；PRPF19的异常表达可能与肿瘤发生有关。然而，PRPF19在肝细胞癌（HCC）中的生物学作用仍不清楚。利用从TCGA、Oncomine和GEO获得的数据，研究PRPF19的表达水平及其在HCC队列的肿瘤免疫浸润、预后和肿瘤进展中的作用。使用各种数据库和工具（UALCAN、TIMER、TISMO和PathCards），我们展示了PFPF19上调的潜在机制、PRPF19相关途径及其在肝癌中的生物学功能。对于HCC，发现PRPF19在单个肿瘤细胞和组织中均上调。此外，PRPF19表达的增加与临床特征显著相关：HCC的晚期、血管侵犯、高甲胎蛋白和预后不良。根据肿瘤免疫分析，我们发现PRPF19与浸润的髓源性抑制细胞（MDSCs）呈正相关。此外，PRPF19高表达的HCC组织微环境具有高度免疫抑制性（T淋巴细胞减少，多个免疫检查点上调）。PRPF19高表达和MDSCs高表达的患者生存预后也较差。TP53突变可能对PRPF19表达有积极影响——PRPF19启动子甲基化降低。通过TF-mRNA网络分析，确定了TC-NER和PCS途径（涉及PRPF19）中的关键转录因子（TFs）。这项工作表明，PRPF19与肿瘤免疫逃逸和进展相关，并作为HCC临床预后较差的预后标志物。因此，这个关键调节因子可作为HCC的潜在治疗靶点。
