Liu Dequan, Liu Lei, Che Xiangyu, Wu Guangzhen
Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Front Cell Dev Biol. 2025 Jan 22;13:1525345. doi: 10.3389/fcell.2025.1525345. eCollection 2025.
Oncogenes are typically overexpressed in tumor tissues and often linked to poor prognosis. However, recent advancements in bioinformatics have revealed that many highly expressed genes in tumors are associated with better patient outcomes. These genes, which act as tumor suppressors, are referred to as "paradoxical genes." Analyzing The Cancer Genome Atlas (TCGA) confirmed the widespread presence of paradoxical genes, and KEGG analysis revealed their role in regulating tumor metabolism. Mechanistically, discrepancies between gene and protein expression-affected by pre- and post-transcriptional modifications-may drive this phenomenon. Mechanisms like upstream open reading frames and alternative splicing contribute to these inconsistencies. Many paradoxical genes modulate the tumor immune microenvironment, exerting tumor-suppressive effects. Further analysis shows that the stage- and tumor-specific expression of these genes, along with their environmental sensitivity, influence their dual roles in various signaling pathways. These findings highlight the importance of paradoxical genes in resisting tumor progression and maintaining cellular homeostasis, offering new avenues for targeted cancer therapy.
癌基因通常在肿瘤组织中过度表达，且常与预后不良相关。然而，生物信息学的最新进展表明，肿瘤中许多高表达基因与患者更好的预后相关。这些作为肿瘤抑制因子的基因被称为“矛盾基因”。对癌症基因组图谱（TCGA）的分析证实了矛盾基因的广泛存在，KEGG分析揭示了它们在调节肿瘤代谢中的作用。从机制上讲，受转录前和转录后修饰影响的基因与蛋白质表达之间的差异可能导致这种现象。上游开放阅读框和可变剪接等机制导致了这些不一致性。许多矛盾基因调节肿瘤免疫微环境，发挥肿瘤抑制作用。进一步分析表明，这些基因的阶段特异性和肿瘤特异性表达以及它们对环境的敏感性，影响了它们在各种信号通路中的双重作用。这些发现突出了矛盾基因在抵抗肿瘤进展和维持细胞稳态中的重要性，为靶向癌症治疗提供了新途径。
