Circ_0007142 downregulates miR‐874‐3p‐mediated GDPD5 on colorectal cancer cells

癌变 细胞凋亡 癌症研究 小RNA 化学 流式细胞术 免疫印迹 下调和上调 基因沉默 结直肠癌 程序性细胞死亡 分子生物学 细胞 体内 生物 癌症 细胞生长 基因 生物化学 生物技术 遗传学
作者
Yueqing Wang,Chen Hongshu,Xueling Wei
出处
期刊:European Journal of Clinical Investigation [Wiley]
卷期号:51 (7) 被引量:53
标识
DOI:10.1111/eci.13541
摘要

Ferroptosis is an iron-dependent and oxidative cell death form. Recent studies suggested that circular RNAs (circRNAs) regulated ferroptosis in tumour cells. Circ_0007142 was identified as a carcinogenic molecule in colorectal cancer (CRC), but its function on ferroptosis in CRC remains unknown.Circ_0007142, microRNA-874-3p (miR-874-3p) and glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) levels were assayed using the quantitative real-time polymerase chain reaction (qRT-PCR). Cell survival and proliferation were measured by Cell Counting Kit-8 (CCK-8) assay. Protein detection was performed by Western blot. Cell apoptosis was analysed by flow cytometry. Ferroptosis was assessed by iron accumulation and oxidative stress. Target binding was evaluated by dual-luciferase reporter assay. In vivo research was conducted by tumour xenograft in mice.Circ_0007142 was overexpressed in CRC. After expression inhibition of circ_0007142, proliferation was reduced, while apoptosis and ferroptosis were facilitated in CRC cells. Mechanically, circ_0007142 was found as a miR-874-3p sponge and miR-874-3p inhibitor eliminated the regulation of si-circ_0007142 in CRC cells. MiR-874-3p targeted GDPD5 and upregulation of GDPD5 reversed the miR-874-3p-triggered tumour inhibition and ferroptosis promotion in CRC cells. Moreover, GDPD5 was regulated by the circ_0007142/miR-874-3p axis. Circ_0007142 also affected CRC tumorigenesis in vivo through the regulation of miR-874-3p and GDPD5.All these findings proved that circ_0007142/miR-874-3p/GDPD5 axis regulated tumorigenesis and ferroptosis of CRC cells. Circ_0007142 might be an available marker for ferroptosis in CRC therapy.
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