Breast Internal Medicine Department, The 3rd Affiliated Teaching Hospital of XinJiang Medical University(Affiliated Tumor Hospital), Urumqi, China.
Bioengineered. 2022 Apr;13(4):8076-8086. doi: 10.1080/21655979.2022.2052672.
Endoplasmic reticulum stress (ERS) is associated with breast cancer progression. However, the potential role of ribosomal protein L5 (RPL5) on ERS in breast cancer remains unclear. This study aimed to determine the role of RPL5/E2F transcription factor 1 (E2F1) in breast cancer. It was found that RPL5 was downregulated in breast cancer cells and tissues. Additionally, overexpression of RPL5 inhibited cell proliferation. Moreover, the levels of ERS and autophagy markers were estimated using western blotting. Overexpression of RPL5 induced ERS and suppressed autophagy. Additionally, RPL5 downregulated E2F1, which was overexpressed in breast cancer cells. However, E2F1 knockdown promoted the transcriptional activation of glucose regulated protein 78 (GRP78), suppressed ERS response, and promoted autophagy. Rescue assays indicated that the effects of RPL5 on ERS and autophagy were abolished by E2F1. Taken together, RPL5 inhibited the growth of breast cancer cells by modulating ERS and autophagy via the regulation of E2F1. These findings suggest that RPL5 has a tumor-suppressive effect in breast cancer.
内质网应激（ERS）与乳腺癌的进展有关。然而，核糖体蛋白 L5（RPL5）在乳腺癌中对 ERS 的潜在作用尚不清楚。本研究旨在确定 RPL5/E2F 转录因子 1（E2F1）在乳腺癌中的作用。结果发现，RPL5 在乳腺癌细胞和组织中表达下调。此外，RPL5 的过表达抑制了细胞增殖。此外，还使用 Western blot 测定了 ERS 和自噬标志物的水平。RPL5 的过表达诱导 ERS 并抑制自噬。此外，RPL5 下调了在乳腺癌细胞中过表达的 E2F1。然而，E2F1 的敲低促进了葡萄糖调节蛋白 78（GRP78）的转录激活，抑制了 ERS 反应，并促进了自噬。挽救实验表明，E2F1 消除了 RPL5 对 ERS 和自噬的影响。总之，RPL5 通过调节 E2F1 来调节 ERS 和自噬，从而抑制乳腺癌细胞的生长。这些发现表明 RPL5 在乳腺癌中具有肿瘤抑制作用。
