Department of General Surgery, The Affiliated Taian City Central Hospital of Qingdao University, Qingdao, China
Department of Hepatobiliary Surgery, The Affiliated Taian City Central Hospital of Qingdao University, Taian, China
Balkan Med J. 2023 Jan 23;40(1):21-27. doi: 10.4274/balkanmedj.galenos.2022.2022-7-80. Epub 2022 Nov 18.
The hypoxia-induced Warburg effect promotes colorectal cancer malignancy with altered circular RNA (circRNA) expression.
To investigate the association with the Warburg effect in colorectal cancer and whether has_circ_0006508 can be induced by hypoxia.
In vitro cell lines and human-sample study.
The biological functions of circ_0006508 and miR-1272 in the viability, colony formation, and glycolysis under hypoxic conditions were determined by loss-of-function and gain-of-function experiments. The chromatin immunoprecipitation assay was used to demonstrate the direct binding between circ_0006508 promoters and hypoxia-inducible factor 1α (HIF-1α). Transcription activity was subjected to the Luciferase reporter assay. The correlation of circ_0006508 and miR-1272 with overall survival was determined with the Kaplan-Meier analysis.
Upregulated circ_0006508 and downregulated miR-1272 were observed in colorectal cancer samples, which was associated with the TNM stage and overall survival. Functional assays demonstrated that the hypoxia-induced upregulated circ_0006508 and downregulated miR-1272 promoted the viability and Warburg effect of colorectal cancer in vitro. Mechanistically, HIF-1α-induced circ_0006508 could directly sponge miR-1272, which played a suppressive role in glycolysis.
Circ_0006508-mediated miR-1272 inhibition could promote the malignant behaviors of colorectal cancer with an upregulated Warburg effect.
缺氧诱导的瓦博格效应促进结直肠癌恶性转化，改变环状 RNA（circRNA）表达。
研究与结直肠癌瓦博格效应的相关性，以及 circ_0006508 是否可被缺氧诱导。
体外细胞系和人体样本研究。
通过功能丧失和获得功能实验，确定 circ_0006508 和 miR-1272 在缺氧条件下对细胞活力、集落形成和糖酵解的影响。染色质免疫沉淀实验用于证明 circ_0006508 启动子与缺氧诱导因子 1α（HIF-1α）之间的直接结合。转录活性通过荧光素酶报告基因检测。Kaplan-Meier 分析确定 circ_0006508 和 miR-1272 与总生存期的相关性。
在结直肠癌样本中观察到 circ_0006508 上调和 miR-1272 下调，与 TNM 分期和总生存期相关。功能分析表明，缺氧诱导的 circ_0006508 上调和 miR-1272 下调促进了结直肠癌细胞在体外的活力和瓦博格效应。机制上，HIF-1α诱导的 circ_0006508 可直接与 miR-1272 结合，后者在糖酵解中发挥抑制作用。
Circ_0006508 介导的 miR-1272 抑制可促进瓦博格效应上调的结直肠癌恶性行为。
