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Circ_0007142 downregulates miR‐874‐3p‐mediated GDPD5 on colorectal cancer cells
Author(s) -
Wang Yueqing,
Chen Hongshu,
Wei Xueling
Publication year - 2021
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.13541
Subject(s) - carcinogenesis , apoptosis , cancer research , chemistry , microrna , cell growth , flow cytometry , western blot , downregulation and upregulation , gene silencing , colorectal cancer , programmed cell death , microbiology and biotechnology , cell , in vivo , biology , cancer , gene , biochemistry , genetics
Background 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. Methods 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. Results 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. Conclusion 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.