RPN1 通过激活 PI3K/AKT/mTOR 信号通路促进乳腺癌细胞的增殖和侵袭

Wei-juan Shen, Yi Zhang
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摘要

核糖蛋白 I(RPN1)是 N-寡糖基转移酶复合物的一部分,在多种癌症的发展过程中起着至关重要的作用。然而,它在乳腺癌中的生物学作用尚未完全明确。本研究利用 RT-qPCR 技术检测了 RPN1 在乳腺癌组织和乳腺癌细胞系(MCF7)中的表达水平。通过 shRNA 下调 RPN1 的表达后,研究了 RPN1 对 MCF7 细胞增殖、迁移和侵袭的影响。我们从机制上评估了RPN1对PI3K/ AKT/mTOR信号通路的影响。我们发现,与邻近的非肿瘤组织或 MCF10A 细胞相比,RPN1 在乳腺癌组织和细胞中的水平上调。敲除 RPN1 可诱导 MCF7 细胞凋亡,并减少其增殖、迁移和侵袭。此外,RPN1基因敲除降低了p-PI3K/PI3K、p-AKT/AKT和p-mTOR/mTOR的水平,而PI3K激活剂740Y-P可以挽救这些水平。740Y-P 还逆转了 RPN1 敲除对 MCF7 细胞凋亡、增殖、迁移和侵袭的影响。综上所述,RPN1 通过 PI3K/AKT/mTOR 信号通路促进乳腺癌细胞的增殖、迁移和侵袭。
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RPN1 promotes the proliferation and invasion of breast cancer cells by activating the PI3K/AKT/mTOR signaling pathway

Ribophorin I (RPN1), a part of an N-oligosaccharyl-transferase complex, plays a vital role in the development of multiple cancers. However, its biological role in breast cancer has not been completely clarified. The RPN1 expression level was measured in breast cancer tissues and breast cancer cell lines (MCF7) using RT-qPCR. After down-regulating RPN1 expression by shRNA, the effects of RPN1 on the proliferation, migration and invasion of MCF7 cells were examined. Mechanistically, we assessed the effect of RPN1 on the PI3K/ AKT/mTOR signaling pathway. We found that RPN1 level was up-regulated in breast cancer tissues and cells compared with adjacent non-tumor tissues or MCF10A cells. RPN1 knockdown induced apoptosis and attenuated the proliferation, migration, and invasion of MCF7 cells. Moreover, RPN1 knockdown lowered the levels of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR, which were rescued by 740Y-P, a PI3K activator. 740Y-P also reversed the effects of RPN1 knockdown on apoptosis, proliferation, migration, and invasion in MCF7 cells. Taken together, RPN1 promotes the proliferation, migration, and invasion of breast cancer cells via the PI3K/AKT/mTOR signaling pathway.

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