Cancer Genetics and Epigenetics, 2025, Vol.13, No.1, 21-31 http://medscipublisher.com/index.php/cge 24 can enhance cell proliferation ability, promote differentiation arrest and inhibit programmed death. These biological processes jointly maintain the malignant characteristics of tumors. Experiments have confirmed that inhibiting PI3K activity can effectively arrest the process of the G1 phase of the cell cycle and significantly down-regulate the expression of related regulatory proteins. It is notable that the continuous activation of this pathway is closely related to endocrine therapy resistance. Its signal transduction can bypass the androgen receptor-dependent pathway, enabling the tumor to survive in a low androgen environment (Pungsrinont et al., 2021). More complex is that the interaction of this pathway with signal networks such as AR and WNT forms a compensatory mechanism, which requires the development of more selective targeted intervention strategies (Shorning et al., 2020). 4.2 Regulation of cell behavior by Wnt/β-catenin signaling Abnormalities in the Wnt/β-catenin pathway are important mechanisms driving tumor progression. The dysregulation of this pathway leads to the abnormal accumulation of β-catenin protein, thereby activating the key genes that regulate cell proliferation and differentiation (Kypta and Waxman, 2012). Its activation status was significantly correlated with malignant phenotypes such as enhanced tumor invasiveness and epithelial-mesenchymal transition. The study also found that miR-182 could aggravate the abnormal Wnt/β-catenin signaling by inhibiting the negative regulatory factors of the pathway (Wang et al., 2018). The therapeutic exploration for this pathway faces dual challenges, it is necessary to overcome the complexity of the pathway itself and handle its interaction with networks such as PI3K/AKT (Zhang and Wang, 2020; Ma et al., 2021). At present, the research focus is concentrated on developing specific inhibitors to achieve precise intervention by regulating key node molecules. 4.3 Clinical significance of DNA repair defects Dysfunction of the DNA damage response system plays an important role in the evolution of prostate cancer. Defects in the repair mechanism lead to an increase in genomic instability, which is closely related to poor prognosis and failure of traditional treatments. It is notable that abnormal DNA repair often forms a synergistic effect with pathways such as PI3K/AKT and Wnt, jointly promoting disease progression (Figure 1) (Chen et al., 2020). Figure 1 SNHG1 binding EZH2 activates PI3K/AKT/mTOR and Wnt/β-catenin signaling pathways in LNCap and PC-3 cells (Adopted from Chen et al., 2020) Image caption: (A) Western blot was used to detect the protein expression levels of PI3K/AKT/mTOR signaling pathway-related proteins p-PI3K, p-AKT, p-mTOR and p-p70S6K in LNCaP and PC3 cells transfected with NC, si-SNHG1, si-EZH2, si-SNHG1+con, si-SNHG1+EZH2; (B) Western blot was used to detect the expression levels of Wnt/β-catenin signaling pathway related proteins Wnt1, β-catenin, c-myc and Cyclin D1 in LNCaP and PC3 cells transfected with NC, si-SNHG1, si-EZH2, si-SNHG1+con and si-SNHG1+EZH2 (Adopted from Chen et al., 2020) Individualized treatment strategies based on molecular typing are emerging. For example, the application of PARP inhibitors in patients with homologous recombination deficiency can significantly improve the therapeutic effect (Chen et al., 2020). An in-depth analysis of the interaction between DNA repair mechanisms and other carcinogenic pathways will provide theoretical support for formulating combined treatment regimens.
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