Xia Zhiliang, Du Dan, Zhang Zhi, Liu Zonglai, Hu Zhonggui, Li Xinyu, Guo Xiong, He Ziqiu
Department of Urology, Second People's Hospital of China Three Gorges University, Yichang, China.
Transl Androl Urol. 2024 Nov 30;13(11):2601-2616. doi: 10.21037/tau-24-304. Epub 2024 Nov 28.
Prostate cancer is a major cause of cancer-related morbidity and mortality in men globally. The pathogenesis involves complex interactions between genetic mutations and environmental factors, activating multiple signaling pathways, especially Wnt/β-catenin, PI3K/Akt, and NF-κB pathways. Tumor suppressor genes and are key inhibitors of these pathways, crucial in suppressing tumor growth and metastasis. This review synthesizes current knowledge on and in prostate cancer, focusing on their biological functions, regulatory mechanisms, and therapeutic potential.
A comprehensive literature review was conducted, examining studies on the molecular biology of and , their expression in prostate cancer, and their impact on processes like proliferation, apoptosis, migration, and invasion.
: (I) Inhibition of Wnt/β-catenin signaling: binds to Wnt ligands, preventing receptor interaction and reducing and expression. (II) Promotion of apoptosis: downregulates anti-apoptotic proteins (e.g., ) and upregulates pro-apoptotic proteins (e.g., ), promoting both intrinsic and extrinsic apoptotic pathways. (III) Suppression of epithelial-mesenchymal transition (EMT) and metastasis: inhibits EMT, reduces cell migration, and modulates matrix metalloproteinases (MMPs) to maintain extracellular matrix (ECM) integrity. : (I) Regulation of signaling pathways: modulates Wnt/β-catenin, PI3K/Akt, and NF-κB pathways, reducing cell proliferation. (II) Enhancement of apoptosis: increases activity and upregulates and while reducing apoptosis inhibitors. (III) Inhibition of cell migration and invasion: suppresses EMT, cytoskeletal dynamics proteins like and , and reduces MMPs, limiting invasiveness.
The tumor suppressor functions of and are critical in the context of prostate cancer. Their ability to inhibit key signaling pathways and promote apoptosis highlights their potential as therapeutic targets. Future research should focus on developing strategies to restore their expression and function, including epigenetic therapies, gene therapy, and small molecule inhibitors. Such approaches could significantly enhance the efficacy of existing treatments and improve patient outcomes.
前列腺癌是全球男性癌症相关发病和死亡的主要原因。其发病机制涉及基因突变与环境因素之间的复杂相互作用，激活多种信号通路，尤其是Wnt/β-连环蛋白、PI3K/Akt和NF-κB通路。肿瘤抑制基因[基因名称未给出]和[基因名称未给出]是这些通路的关键抑制剂，对抑制肿瘤生长和转移至关重要。本综述综合了目前关于[基因名称未给出]和[基因名称未给出]在前列腺癌中的知识，重点关注它们的生物学功能、调控机制和治疗潜力。
进行了全面的文献综述，研究了[基因名称未给出]和[基因名称未给出]的分子生物学、它们在前列腺癌中的表达以及它们对增殖、凋亡、迁移和侵袭等过程的影响。
[基因名称未给出]：（I）抑制Wnt/β-连环蛋白信号传导：[基因名称未给出]与Wnt配体结合，阻止受体相互作用并降低[相关蛋白名称未给出]和[相关蛋白名称未给出]的表达。（II）促进凋亡：[基因名称未给出]下调抗凋亡蛋白（如[蛋白名称未给出]）并上调促凋亡蛋白（如[蛋白名称未给出]），促进内源性和外源性凋亡途径。（III）抑制上皮-间质转化（EMT）和转移：[基因名称未给出]抑制EMT，减少细胞迁移，并调节基质金属蛋白酶（MMPs）以维持细胞外基质（ECM）的完整性。[基因名称未给出]：（I）信号通路的调节：[基因名称未给出]调节Wnt/β-连环蛋白、PI3K/Akt和NF-κB通路，减少细胞增殖。（II）增强凋亡：[基因名称未给出]增加[相关蛋白名称未给出]的活性并上调[相关蛋白名称未给出]和[相关蛋白名称未给出]，同时减少凋亡抑制剂。（III）抑制细胞迁移和侵袭：[基因名称未给出]抑制EMT、细胞骨架动力学蛋白如[蛋白名称未给出]和[蛋白名称未给出]，并减少MMPs，限制侵袭性。
[基因名称未给出]和[基因名称未给出]的肿瘤抑制功能在前列腺癌背景下至关重要。它们抑制关键信号通路和促进凋亡的能力突出了它们作为治疗靶点的潜力。未来的研究应专注于开发恢复它们表达和功能的策略，包括表观遗传疗法、基因疗法和小分子抑制剂。这些方法可以显著提高现有治疗的疗效并改善患者预后。
