Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Cell Death Dis. 2021 Jul 9;12(7):690. doi: 10.1038/s41419-021-03960-w.
Emerging evidence has declared that Proteasome 26S subunit ATPase 2 (PSMC2) is involved in tumor progression. However, its role in breast cancer has not been investigated. Therefore, we sought to establish a correlation between breast cancer and PSMC2. PSMC2 expression in tissues was detected by immunohistochemistry. Loss-of-function study was used to evaluate the effects of PSMC2 knockdown in cell proliferation, apoptosis and migration. A gene microarray was performed to explore the potential downstream of PSMC2 with the help of Ingenuity Pathway Analysis (IPA). The effects of the PSMC2/PLAU axis on breast cancer were examined in vitro. Compared to para-cancer tissues, PSMC2 level was considerably elevated in breast cancer, which was significantly correlated with tumor grade. Knockdown of PSMC2 suppressed breast cancer progression in vitro and in vivo. The mechanistic research revealed that PSMC2 promotes the development and progression of human breast cancer through interacting with PLAU. Outcomes of our study showed that overexpression of PSMC2 provide tumorigenic and metastatic advantages in breast cancer, which may involve the regulation of PLAU. This study not only reveals a critical mechanism of breast cancer development, but also provides a promising therapeutic target for breast cancer treatment.
越来越多的证据表明蛋白酶体 26S 亚基 ATP 酶 2 (PSMC2) 参与肿瘤进展。然而，其在乳腺癌中的作用尚未被研究。因此，我们试图建立乳腺癌与 PSMC2 之间的相关性。通过免疫组织化学检测组织中 PSMC2 的表达。利用失活功能研究来评估 PSMC2 敲低对细胞增殖、凋亡和迁移的影响。借助 IPA 进行基因微阵列分析以探索 PSMC2 的潜在下游靶点。在体外研究 PSMC2/PLAU 轴对乳腺癌的影响。与癌旁组织相比，PSMC2 在乳腺癌中的水平显著升高，且与肿瘤分级显著相关。PSMC2 敲低抑制了乳腺癌在体外和体内的进展。机制研究表明，PSMC2 通过与 PLAU 相互作用促进了人类乳腺癌的发生和发展。我们的研究结果表明，PSMC2 的过表达为乳腺癌提供了致瘤和转移优势，这可能涉及 PLAU 的调节。这项研究不仅揭示了乳腺癌发展的关键机制，而且为乳腺癌的治疗提供了一个有前途的治疗靶点。
