Jiang Yun, Cui Jingyi, Cui Ming, Jing Rongrong
Department of Clinical Laboratory, Wuxi 9th People's Hospital Affiliated to Soochow University, China; Department of Clinical Laboratory, Affiliated Hospital of Nantong University, Medical school of Nantong University, China.
Department of Clinical Laboratory, Affiliated Hospital of Nantong University, Medical school of Nantong University, China.
Pathol Res Pract. 2023 Aug;248:154646. doi: 10.1016/j.prp.2023.154646. Epub 2023 Jun 28.
Ferroptosis is a form of regulated cell death that occurs depending on iron and reactive oxygen species (ROS), but the underlying molecular mechanisms remain poorly understood. The aim of our study was to investigate the role of solute carrier family 7 member 11(SLC7A11) in the progression of gastric cancer (GC) and its molecular mechanism.
The expression of SLC7A11 in GC was detected by real-time fluorescence quantitative polymerase chain reaction (RT-PCR), immunohistochemistry (IHC) and western blot. SLC7A11 interference and overexpression vector was constructed in vitro, transfected into GC cells, and the high efficiency plasmid vector fragment was screened.CCK-8 assay was used to detect the effect of cell proliferation. The migration ability of cells was detected by transwell assay. The mitochondrial structure was observed by transmission electron microscopy.CCK-8 assay was also used to detect the effect of SLC7A11 on the growth inhibition rate of ferroptosis in GC cells. The level of malondialdehyde (MDA), the ultimate product of lipid peroxidation, was detected by micro-method. The effect of SLC7A11 on PI3K/AKT signaling pathway was detected by Western blot.
SLC7A11 was significantly overexpressed in GC tissues than that in adjacent tissues. Knockdown of SLC7A11 inhibits cell proliferation, cell migration and invasion of GC, and increases the sensitivity of ferroptosis via moderating ROS and lipid peroxidation. Besides, overexpression of the SLC7A11 in GC cells reverses erastin-induced ferroptosis partially. Mechanistically, we reveal that suppression of SCL7A11 leads to inactivity of PI3K/AKT signaling pathway and further enhancing ferroptosis related lipid peroxidation, and thereby inhibiting GC progression.
SLC7A11 plays an oncogene role in malignant progression of GC. SLC7A11 reversely regulates ferroptosis of GC cells by activating PI3K/AKT signaling pathway. Silencing SLC7A11 expression can inhibit the progression of GC.
铁死亡是一种依赖铁和活性氧（ROS）发生的程序性细胞死亡形式，但其潜在分子机制仍知之甚少。本研究旨在探讨溶质载体家族7成员11（SLC7A11）在胃癌（GC）进展中的作用及其分子机制。
采用实时荧光定量聚合酶链反应（RT-PCR）、免疫组织化学（IHC）和蛋白质免疫印迹法检测GC中SLC7A11的表达。体外构建SLC7A11干扰及过表达载体，转染GC细胞并筛选高效质粒载体片段。采用CCK-8法检测细胞增殖情况。通过Transwell实验检测细胞迁移能力。利用透射电子显微镜观察线粒体结构。CCK-8法还用于检测SLC7A11对GC细胞铁死亡生长抑制率的影响。采用微量法检测脂质过氧化终产物丙二醛（MDA）水平。通过蛋白质免疫印迹法检测SLC7A11对PI3K/AKT信号通路的影响。
与癌旁组织相比，SLC7A11在GC组织中显著过表达。敲低SLC7A11可抑制GC细胞增殖、迁移和侵袭，并通过调节ROS和脂质过氧化增加铁死亡敏感性。此外，GC细胞中SLC7A11过表达可部分逆转erastin诱导的铁死亡。机制上，我们发现抑制SCL7A11会导致PI3K/AKT信号通路失活，并进一步增强铁死亡相关的脂质过氧化，从而抑制GC进展。
SLC7A11在GC恶性进展中发挥癌基因作用。SLC7A11通过激活PI3K/AKT信号通路反向调节GC细胞的铁死亡。沉默SLC7A11表达可抑制GC进展。
