miR-539 activates the SAPK/JNK signaling pathway to promote ferropotosis in colorectal cancer by directly targeting TIPE.
Yan YangZeyang LinZhaopu HanZhengxin WuJianyu HuaRui ZhongRuidan ZhaoHonggang RanKaiyong QuHongfei HuangHuamei TangJiyi HuangZhongchen LiuXuehui HongZhihai PengGuohong ZhuangPublished in: Cell death discovery (2021)
Colorectal cancer (CRC) is a common tumor that harms human health with a high recurrence rate. It has been reported that the expression of microRNA-539 (miR-539) is low in several types of cancer, including CRC. Tumor necrosis factor (TNF)-α-induced protein 8 (TNFAIP8/TIPE) is highly expressed in CRC and promotes the proliferation, migration and angiogenesis of CRC. However, the relationship between miR-539 and TIPE and the mechanisms by which they regulate the proliferation of CRC remain to be explored. We aimed to investigate the functions and mechanisms of miR-539 in CRC proliferation. Functionally, miR-539 can bind to and regulate the expression of TIPE, and miR-539 activates SAPK/JNK to downregulate the expression of glutathione peroxidase 4 (GPX4) and promote ferroptosis. Our data reveal the novel role of miR-539 in regulating ferroptosis in CRC via activation of the SAPK/JNK axis, providing new insight into the mechanism of abnormal proliferation in CRC and a novel potential therapeutic target for advanced CRC.
Keyphrases
- signaling pathway
- long non coding rna
- cell proliferation
- poor prognosis
- long noncoding rna
- cell death
- human health
- induced apoptosis
- pi k akt
- risk assessment
- rheumatoid arthritis
- epithelial mesenchymal transition
- binding protein
- endothelial cells
- gene expression
- oxidative stress
- deep learning
- nitric oxide
- single cell
- hydrogen peroxide
- high glucose
- artificial intelligence
- drug induced
- free survival