环状 RNA circEPSTI1 通过 miR-375/409-3P/515-5p-SLC7A11 轴加速宫颈癌进展。
Circular RNA circEPSTI1 accelerates cervical cancer progression via miR-375/409-3P/515-5p-SLC7A11 axis.
机构信息
Department of Critical Care Medicine, Hengyang Maternal and Child Health Hospital, Hengyang 421001, Hunan Province, China.
Yueyang Maternal and Child Health Hospital, Yueyang 414000, Hunan Province, China.
出版信息
Aging (Albany NY). 2021 Feb 2;13(3):4663-4673. doi: 10.18632/aging.202518.
BACKGROUND
Circular RNAs (circRNAs) is one kind of non-coding RNAs (ncRNAs) and exert crucial functions in biological processes and intracellular gene expression modulation. However, the biological roles and expression status of the majority of circRNAs still remain unknown in cervical cancer.
RESULTS
In this study, circEPSTI1 (hsa_circRNA_000479) was significantly upregulated in cervical cancer. We first discovered the impact of circRNA on cell ferroptosis in cervical cancer. Interestingly, circEPSTI1 attenuates the effect of ferritin which is mediated by SLC7A11 based on lipid peroxidation measurements and reduced glutathione and glutathione (GSH/GSSG) assay.
CONCLUSIONS
circEPSTI1-miR-375/409-3P/515-5p-SLC7A11 axis affected the proliferation of cervical cancer via the competing endogenous RNAs (ceRNA) mechanism and was relative to ferroptosis. Our findings provided experimental evidences which revealed that circEPSTI1 might act as a new and useful biomarker for monitoring and treatment target for cervical cancer.
METHODS
The expression of circEPSTI1 was examined in cervical cancer cells. Then, we observed the impact of circEPSTI1 expression on the proliferation of cervical cancer by loss-of-function assays both and . RIP and luciferase reporter assay revealed that circEPSTI1 sponges miR-375, miR-409-3p and miR-515-5p to upregulate SLC7A11 expression. We applied mouse xenograft experiments in mice to validate our results.
背景
环状 RNA（circRNAs）是一种非编码 RNA（ncRNAs），在生物过程和细胞内基因表达调控中发挥着关键作用。然而，在宫颈癌中，大多数 circRNAs 的生物学功能和表达状态仍然未知。
结果
在本研究中，环状 EPSTI1（hsa_circRNA_000479）在宫颈癌中显著上调。我们首次发现 circRNA 对宫颈癌细胞铁死亡的影响。有趣的是，circEPSTI1 通过基于脂质过氧化测量和还原型谷胱甘肽和谷胱甘肽（GSH/GSSG）测定的 SLC7A11 介导的铁蛋白来减弱其作用。
结论
circEPSTI1-miR-375/409-3P/515-5p-SLC7A11 轴通过竞争性内源性 RNA（ceRNA）机制影响宫颈癌的增殖，并与铁死亡有关。我们的研究结果提供了实验证据，表明 circEPSTI1 可能作为宫颈癌监测和治疗靶点的新的有用的生物标志物。
方法
检测宫颈癌细胞中 circEPSTI1 的表达。然后，我们通过功能丧失实验观察 circEPSTI1 表达对宫颈癌增殖的影响。RIP 和荧光素酶报告基因实验表明，circEPSTI1 作为 miR-375、miR-409-3p 和 miR-515-5p 的海绵来上调 SLC7A11 的表达。我们在小鼠异种移植实验中验证了我们的结果。
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