环状 RNA PLOD2 通过 miR-513a-5p/SIX1/LDHA 轴促进结肠癌的发生和瓦博格效应。
circRNA PLOD2 promotes tumorigenesis and Warburg effect in colon cancer by the miR-513a-5p/SIX1/LDHA axis.
机构信息
Clinical Laboratory, The Third Xiangya Hospital of Central South University, Changsha, China.
Radiation Oncology, The Second Affiliated Hospital Of Xi'an Jiaotong University, Xi'an, China.
出版信息
Cell Cycle. 2022 Dec;21(23):2484-2498. doi: 10.1080/15384101.2022.2103339. Epub 2022 Sep 7.
Increasing evidence has proved that circRNAs might act as potential biomarkers for tumor diagnosis and prognosis. However, the functions and mechanisms of multiple circRNAs in colon cancer remains unclear. Here, we found circPLOD2 was dramatically upregulated in colon cancer tissue and cell lines. In vitro CCK-8, colony formation and transwell assays, and in vivo tumor transplantation assay were performed and explored that circPLOD2 might promote tumor proliferation, migration and invasion in vitro and in vivo. Moreover, based on the analysis of RNA pull-down, RNA immunoprecipitation, luciferase and rescued assays, we confirmed that the interactions between circPLOD2, miR-513a-5p and SIX1. It suggested that circPLOD2 acted as a sponge of miR-513a-5p to regulate the activation of the target gene SIX1. In addition, as a key transcription factor of Warburg effect related genes, SIX1 was proved to enhance the transcriptional expression of LDHA by chromatin immunoprecipitation assay, thereby regulating glycolysis in colon cancer cells. Therefore, we identified that circPLOD2 promoted colon cancer progression through miR-513a-5p/SIX1/LDHA axis, and acted as a new biomarker for colon cancer prognosis and treatment.
越来越多的证据证明 circRNAs 可能作为肿瘤诊断和预后的潜在生物标志物。然而，多种 circRNAs 在结肠癌中的功能和机制仍不清楚。在这里，我们发现 circPLOD2 在结肠癌组织和细胞系中显著上调。我们进行了体外 CCK-8、集落形成和 Transwell 检测以及体内肿瘤移植实验，结果表明 circPLOD2 可能促进肿瘤在体外和体内的增殖、迁移和侵袭。此外，基于 RNA 下拉、RNA 免疫沉淀、荧光素酶和挽救实验的分析，我们证实了 circPLOD2、miR-513a-5p 和 SIX1 之间的相互作用。这表明 circPLOD2 作为 miR-513a-5p 的海绵分子，调节靶基因 SIX1 的激活。此外，作为与 Warburg 效应相关基因的关键转录因子，SIX1 通过染色质免疫沉淀实验被证明可以增强 LDHA 的转录表达，从而调节结肠癌细胞中的糖酵解。因此，我们确定 circPLOD2 通过 miR-513a-5p/SIX1/LDHA 轴促进结肠癌的进展，并作为结肠癌预后和治疗的新生物标志物。
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