Key Laboratory of Pathobiology, State Ethnic Affairs Commission, Yanbian University, Yanji, China.
Department of Pathology, Medical School of Yanbian University, Yanji, China.
Mol Carcinog. 2024 Dec;63(12):2392-2400. doi: 10.1002/mc.23817. Epub 2024 Sep 11.
Polyadenylate-binding protein-interacting protein 1 (PAIP1) is a protein that modulates translation initiation in eukaryotic cells. Studies have shown that PAIP1 was overexpressed in various type of cancers, and drives cancer progression by promoting cancer cell proliferation, invasion, and migration. In our previous study, we identified that PAIP1 was overexpressed in breast cancer, and the expression was correlated with poor prognosis. However, the biological function of PAIP1 in breast cancer has not been clearly understood. In this study, we constructed PAIP1 specifically silenced breast cancer cells. Then, cell proliferation, cell cycle distribution, and apoptosis were detected in PAIP1 knockdown cells. RNA-seq analysis was performed to predict the downstream target of PAIP1, and the molecular mechanism was explored. As a results, we found that knockdown of PAIP1 repressed cell proliferation, induced cell cycle arrest, and triggers apoptosis. Xenograft mouse model showed that knockdown of PAIP1 inhibits cell growth in vivo. RNA-seq predicted that CCNE2 mRNA was one of the downstream targets of PAIP1. In addition, we identified that knockdown of PAIP1-inhibited cell proliferation through modulating cyclin E2 expression. Mechanically, knockdown of PAIP1 reduces the expression of cyclin E2 by regulating the mRNA stability of cyclin E2. Moreover, in breast cancer tissues, we found that the expression of PAIP1 was positively correlated with cyclin E2. Taken together, our findings establish the role and mechanism of PAIP1 in breast cancer progression, indicating that PAIP1 would be a new therapeutic target for breast cancer treatment.
多聚腺苷酸结合蛋白相互作用蛋白 1（PAIP1）是一种在真核细胞中调节翻译起始的蛋白质。研究表明，PAIP1 在各种类型的癌症中过表达，并通过促进癌细胞增殖、侵袭和迁移来推动癌症进展。在我们之前的研究中，我们发现 PAIP1 在乳腺癌中过表达，并且表达与预后不良相关。然而，PAIP1 在乳腺癌中的生物学功能尚不清楚。在这项研究中，我们构建了 PAIP1 特异性沉默的乳腺癌细胞。然后，在 PAIP1 敲低细胞中检测细胞增殖、细胞周期分布和细胞凋亡。进行 RNA-seq 分析以预测 PAIP1 的下游靶标，并探索分子机制。结果发现，敲低 PAIP1 抑制细胞增殖，诱导细胞周期停滞，并触发细胞凋亡。异种移植小鼠模型表明，敲低 PAIP1 抑制体内细胞生长。RNA-seq 预测 CCNE2 mRNA 是 PAIP1 的下游靶标之一。此外，我们发现敲低 PAIP1 通过调节细胞周期蛋白 E2 的表达来抑制细胞增殖。机制上，敲低 PAIP1 通过调节细胞周期蛋白 E2 的 mRNA 稳定性来降低细胞周期蛋白 E2 的表达。此外，在乳腺癌组织中，我们发现 PAIP1 的表达与细胞周期蛋白 E2 的表达呈正相关。总之，我们的研究结果确立了 PAIP1 在乳腺癌进展中的作用和机制，表明 PAIP1 可能成为治疗乳腺癌的新靶点。
