Shu Hang, Chen Xiaoyu, Zhao Jie, Li Ping, Sun Zhen
Traditional Chinese Medicine Department, People's Liberation Army Air Force Hangzhou Special Service Recuperation Center Nanjing 210000, Jiangsu, China.
Am J Transl Res. 2024 Nov 15;16(11):6346-6364. doi: 10.62347/JRDP4018. eCollection 2024.
Cancer remains one of the leading causes of mortality worldwide, characterized by uncontrolled cell proliferation and metastasis. Protein Inhibitor of Activated STAT (PIAS) family genes, comprising PIAS1, PIAS2, PIAS3, and PIAS4, are emerging as significant players in cancer biology due to their roles in SUMOylation, transcriptional regulation, and modulation of signal transduction pathways. This study provides a comprehensive analysis of PIAS family genes from a pan-cancer viewpoint.
Detailed in silico analyses using publicly available databases and in vitro analyses involving cell culture, gene knockdown, colony formation, and wound healing assays.
Expression analysis revealed consistent up-regulation of PIAS1, PIAS2, PIAS3, and PIAS4 genes in tumors compared to normal tissues. Univariate Cox regression analyses indicate that high PIAS gene expression correlates with worse overall survival in specific cancers, particularly kidney renal papillary cell carcinoma (KIRP) and liver hepatocellular carcinoma (LIHC). Kaplan-Meier plots further confirm that higher PIAS gene expression is significantly associated with reduced survival probabilities in these cancers. Genetic alteration analysis showed low mutation frequencies in PIAS genes, suggesting their role in cancer progression is likely due to expression regulation rather than genetic mutations. Correlations with immune subtypes, the tumor microenvironment (TME), and immune stimulatory genes highlight the differential expression of PIAS genes across immune landscapes in KIRP and LIHC. Gene enrichment analysis emphasizes the involvement of PIAS genes in crucial cellular processes, including SUMOylation and ubiquitin-mediated proteolysis. Finally, knockdown experiments in HCC-LM3 cells demonstrate that PIAS2 and PIAS3 promote tumor growth and metastasis, reinforcing their potential as therapeutic targets.
This study revealed the multifaceted roles of PIAS genes in KIRP and LIHC biology and their potential as prognostic biomarkers and therapeutic targets.
癌症仍然是全球主要的死亡原因之一，其特征为细胞不受控制的增殖和转移。活化信号转导子和转录激活子的蛋白抑制剂（PIAS）家族基因，包括PIAS1、PIAS2、PIAS3和PIAS4，因其在小泛素相关修饰物化、转录调控和信号转导通路调节中的作用，正在成为癌症生物学中的重要参与者。本研究从泛癌角度对PIAS家族基因进行了全面分析。
使用公开可用数据库进行详细的计算机分析，并进行涉及细胞培养、基因敲低、集落形成和伤口愈合试验的体外分析。
表达分析显示，与正常组织相比，肿瘤中PIAS1、PIAS2、PIAS3和PIAS4基因持续上调。单因素Cox回归分析表明，PIAS基因高表达与特定癌症，特别是肾肾乳头细胞癌（KIRP）和肝细胞癌（LIHC）的总体生存率较差相关。Kaplan-Meier曲线进一步证实，PIAS基因高表达与这些癌症的生存概率降低显著相关。基因改变分析显示PIAS基因的突变频率较低，表明它们在癌症进展中的作用可能是由于表达调控而非基因突变。与免疫亚型、肿瘤微环境（TME）和免疫刺激基因的相关性突出了PIAS基因在KIRP和LIHC免疫格局中的差异表达。基因富集分析强调了PIAS基因参与关键的细胞过程，包括小泛素相关修饰物化和泛素介导的蛋白水解。最后，在HCC-LM3细胞中的敲低实验表明，PIAS2和PIAS3促进肿瘤生长和转移，增强了它们作为治疗靶点的潜力。
本研究揭示了PIAS基因在KIRP和LIHC生物学中的多方面作用及其作为预后生物标志物和治疗靶点的潜力。
