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

Abstract

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.

M6A-Mediated Upregulation of CircMDK Promotes Tumorigenesis and Acts as a Nanotherapeutic Target in Hepatocellular Carcinoma

“…Guo J et al found that miR-346 enhanced Ago2 expression to regulate the activity of other miRNAs and migration and invasion of cervical cancer 31 . It is reported that miR-874-3p expression was abnormally reduced in a variety of cancers, including ovarian cancer 32 , colorectal cancer 33 and HCC 34 . Here, our ndings revealed the signi cance of the interaction of circMDK and miR-346/miR-874-3p in tumorigenesis.…”

Ferroptosis in Cancer Progression: Role of Noncoding RNAs

“…For instance, downregulation of circABCB10 via the miR-326/ CCL5 axis promoted cancer cell ferroptosis and inhibited the progression of rectal cancer [71]. Similarly, another study [70] showed that circ_0007142 was upregulated in CRC, and inhibition of circ_0007142 could promote apoptosis and ferroptosis of CRC cells, resulting in reduced cancer cell proliferation.…”

“…In terms of regulating ferroptosis-related genes, some studies have demonstrated that many ncRNAs play vital roles in regulating the expression of the ferroptosis-related genes [66]. Some ncRNAs regulate ferroptosis in cancer cells by affecting the protein level of ferroptosis-associated genes, such as FSP1 [67], EIF4A1 [68], GABPB1 [69], GDPD5 [70], and CCL5 [71]. A number of ncRNAs could affect both the mRNA and protein levels of ferroptosis-associated genes, such as NRF2 [72], STAT3 [73], ATF4 [74], AURKA [75], and ITGB8 [76].…”

Ferroptosis Holds Novel Promise in Treatment of Cancer Mediated by Non-coding RNAs

“…Currently, only limited reports on the function of circRNAs in ferroptosis have been explored so far Liu Z. et al, 2020;Xu et al, 2020;Zhang H. Y. et al, 2020;Wang et al, 2021;Wu et al, 2021;Zhang et al, 2021a; Table 3). Most of these studies have focused on the sponging effect of circRNAs, while Liu Z. et al have brought insights into the role of circRNA cIARS as a protein scaffold in mediating RNA binding protein AlkB Homolog 5 (ALKBH5) (Liu Z. et al, 2020).…”