Functional Characterization and Prognostic Value of PIAS Family Genes in Liver Hepatocellular Carcinoma.

IF 3.5 4区医学 Q3 ONCOLOGY

Current cancer drug targets Pub Date : 2025-10-17 DOI:10.2174/0115680096390042250929110047

Ahmad Mahmood, Zhayier Musitafa, Shaoib Muhammad, Tiemin Jiang, Rexiati Ruze, Zhang Ruiqing, Erpan Yilihaer, Abuduhaiwaier Abuduhelili, Tuerganaili Aji

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引用次数: 0

Abstract

Introduction: Liver Hepatocellular Carcinoma (LIHC) poses a significant global health burden, necessitating comprehensive molecular investigations to elucidate its pathogenesis and identify potential biomarkers and therapeutic targets.

Methods: This study utilized Bioinformatics and detailed molecular experiments to delve into the expression profiling and epigenetic regulation of PIAS family genes in LIHC, shedding light on their diagnostic, prognostic, and therapeutic implications.

Results: Analysis of clinical specimens revealed a pronounced up-regulation of PIAS1, PIAS2, PIAS3, and PIAS4 genes in LIHC cell lines and tissue samples compared to normal controls, emphasizing their potential as diagnostic biomarkers for LIHC. Furthermore, promoter methylation profiling unveiled significant hypomethylation of PIAS1, PIAS2, PIAS3, and PIAS4 genes in LIHC samples, implicating epigenetic dysregulation in LIHC pathogenesis. Validation using independent TCGA datasets corroborated these findings, emphasizing the robustness of PIAS family genes as diagnostic markers for LIHC. Functional analyses revealed that PIAS1 knockdown in HepG2 cells significantly impaired proliferation and colony formation, while paradoxically enhancing cell migration. These results suggest a dual role for PIAS1 in promoting tumor growth while inhibiting metastatic potential. Prognostic modeling demonstrated the collective impact of dysregulated PIAS family genes on overall survival outcomes in LIHC patients, emphasizing their clinical relevance in prognostic assessments. Furthermore, correlation analysis with immune infiltrates and drug sensitivity profiling revealed intricate interactions and therapeutic implications of PIAS family genes in LIHC.

Discussion: The upregulation and hypomethylation of PIAS1-4 in LIHC suggest their role in tumor initiation and progression. PIAS1 knockdown impaired proliferation but increased migration, indicating a dual role in growth and metastasis. These findings align with poor patient survival linked to PIAS dysregulation. Their association with immune infiltration and drug sensitivity highlights potential for targeted therapies.

Conclusion: This study provides valuable insights into the multifaceted roles of PIAS family genes in LIHC pathogenesis and paves the way for personalized diagnostic and therapeutic interventions.

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肝细胞癌PIAS家族基因的功能特征及预后价值。

肝细胞癌（Liver hepatellular Carcinoma， LIHC）是一种全球性的健康疾病，需要进行全面的分子研究来阐明其发病机制，并确定潜在的生物标志物和治疗靶点。方法：本研究利用生物信息学和详细的分子实验，深入研究PIAS家族基因在LIHC中的表达谱和表观遗传调控，揭示其诊断、预后和治疗意义。结果：临床标本分析显示，与正常对照相比，LIHC细胞系和组织样本中PIAS1、PIAS2、PIAS3和PIAS4基因明显上调，强调了它们作为LIHC诊断生物标志物的潜力。此外，启动子甲基化分析揭示了LIHC样本中PIAS1、PIAS2、PIAS3和PIAS4基因的显著低甲基化，暗示了LIHC发病机制中的表观遗传失调。使用独立的TCGA数据集进行验证证实了这些发现，强调了PIAS家族基因作为LIHC诊断标记的稳健性。功能分析显示，PIAS1敲低在HepG2细胞中显著损害增殖和集落形成，同时矛盾地增强细胞迁移。这些结果表明PIAS1在促进肿瘤生长和抑制转移潜能方面具有双重作用。预后模型显示了PIAS家族基因失调对LIHC患者总体生存结果的总体影响，强调了它们在预后评估中的临床相关性。此外，与免疫浸润和药物敏感性分析的相关分析揭示了PIAS家族基因在LIHC中复杂的相互作用和治疗意义。讨论：PIAS1-4在LIHC中的上调和低甲基化表明它们在肿瘤的发生和发展中起作用。PIAS1敲低抑制了细胞增殖，但增加了迁移，表明在生长和转移中具有双重作用。这些发现与PIAS失调相关的患者生存率较低一致。它们与免疫浸润和药物敏感性的关联突出了靶向治疗的潜力。结论：本研究对PIAS家族基因在LIHC发病机制中的多重作用提供了有价值的见解，并为个性化诊断和治疗干预铺平了道路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current cancer drug targets 医学-肿瘤学

CiteScore

5.40

自引率

0.00%

发文量

105

审稿时长

1 months

期刊介绍： Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes. Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.