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MiR-539 activates the SAPK/JNK signaling pathway to promote ferropotosis in colorectal cancer by directly targeting TIPE.

ABSTRACT: 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.

SUBMITTER: Yang Y 

PROVIDER: S-EPMC8487425 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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miR-539 activates the SAPK/JNK signaling pathway to promote ferropotosis in colorectal cancer by directly targeting TIPE.

Yang Yan Y   Lin Zeyang Z   Han Zhaopu Z   Wu Zhengxin Z   Hua Jianyu J   Zhong Rui R   Zhao Ruidan R   Ran Honggang H   Qu Kaiyong K   Huang Hongfei H   Tang Huamei H   Huang Jiyi J   Liu Zhongchen Z   Hong Xuehui X   Peng Zhihai Z   Zhuang Guohong G  

Cell death discovery 20211002 1

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  ...[more]

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