PSMC4 通过调控 CBX3-EGFR-PI3K-AKT-mTOR 通路促进前列腺癌进展。
PSMC4 promotes prostate carcinoma progression by regulating the CBX3-EGFR-PI3K-AKT-mTOR pathway.
机构信息
Department of Andrology, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
Department of Andrology, Northern Jiangsu People's Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
出版信息
J Cell Mol Med. 2023 Aug;27(16):2437-2447. doi: 10.1111/jcmm.17832. Epub 2023 Jul 12.
Proteasome 26S subunit ATPase 4 (PSMC4) could regulate cancer progression. However, the function of PSMC4 in prostate carcinoma (PCa) progression requires further clarification. In the study, PSMC4 and chromobox 3 (CBX3) levels were verified by TCGA data and tissue microarrays. Cell counting kit-8, cell apoptosis, cell cycle, wound healing, transwell and xenograft tumour model assays were performed to verify biological functions of PSMC4 in PCa. RNA-seq, PCR, western blotting and co-IP assays were performed to verify the mechanism of PSMC4. Results showed that PSMC4 level was significantly increased in PCa tissues, and patients with PCa with a high PSMC4 level exhibited shorter overall survival. PSMC4 knockdown markedly inhibited cell proliferation, cell cycle and migration in vitro and in vivo, and significantly promoted cell apoptosis. Then further study revealed that CBX3 was a downstream target of PSMC4. PSMC4 knockdown markedly reduced CBX3 level, and inhibited PI3K-AKT-mTOR signalling. CBX3 overexpression markedly promoted epidermal growth factor receptor (EGFR) level. Finally, PSMC4 overexpression showed reverse effect in DU145 cells, and the effects of PSMC4 overexpression on cell proliferation, migration and clonal formation were rescued by the CBX3 knockdown, and regulated EGFR-PI3K-AKT-mTOR signalling. In conclusion, PSMC4 could regulate the PCa progression by mediating the CBX3-EGFR-PI3K-AKT-mTOR pathway. These findings provided a new target for PCa treatment.
蛋白酶体 26S 亚基 ATP 酶 4（PSMC4）可调节癌症的进展。然而，PSMC4 在前列腺癌（PCa）进展中的功能需要进一步阐明。在本研究中，通过 TCGA 数据和组织微阵列验证了 PSMC4 和染色质盒 3（CBX3）的水平。通过细胞计数试剂盒-8、细胞凋亡、细胞周期、划痕愈合、Transwell 和异种移植肿瘤模型检测，验证了 PSMC4 在 PCa 中的生物学功能。通过 RNA-seq、PCR、Western blot 和 co-IP 检测，验证了 PSMC4 的作用机制。结果表明，PSMC4 水平在 PCa 组织中明显升高，PSMC4 水平较高的 PCa 患者总生存期较短。PSMC4 敲低显著抑制体外和体内细胞增殖、细胞周期和迁移，并显著促进细胞凋亡。进一步研究表明，CBX3 是 PSMC4 的下游靶标。PSMC4 敲低显著降低 CBX3 水平，并抑制 PI3K-AKT-mTOR 信号通路。CBX3 过表达显著上调表皮生长因子受体（EGFR）水平。最后，在 DU145 细胞中过表达 PSMC4 表现出相反的效果，CBX3 敲低可挽救 PSMC4 过表达对细胞增殖、迁移和克隆形成的影响，并调节 EGFR-PI3K-AKT-mTOR 信号通路。综上所述，PSMC4 可通过介导 CBX3-EGFR-PI3K-AKT-mTOR 通路调节 PCa 进展。这些发现为 PCa 的治疗提供了新的靶点。
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