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微小RNA-539通过直接靶向肿瘤坏死因子α诱导蛋白8样分子2激活应激激活蛋白激酶/应激活化蛋白激酶信号通路，促进结直肠癌铁死亡。

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

作者信息

Yang Yan, Lin Zeyang, Han Zhaopu, Wu Zhengxin, Hua Jianyu, Zhong Rui, Zhao Ruidan, Ran Honggang, Qu Kaiyong, Huang Hongfei, Tang Huamei, Huang Jiyi, Liu Zhongchen, Hong Xuehui, Peng Zhihai, Zhuang Guohong

机构信息

Xiamen Key Laboratory of Regeneration Medicine, Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, Organ Transplantation Institute, School of Medicine, Xiamen University, 4221-122 Xiang An South Road, 361102, Xiamen, China.

Department of Pathology, Zhongshan Hospital Affiliated to Xiamen University, 361001, Xiamen, China.

出版信息

Cell Death Discov. 2021 Oct 2;7(1):272. doi: 10.1038/s41420-021-00659-x.

DOI:10.1038/s41420-021-00659-x
PMID:34601499
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8487425/
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.

摘要

结直肠癌（CRC）是一种常见的危害人类健康且复发率高的肿瘤。据报道，微小RNA-539（miR-539）在包括CRC在内的多种癌症类型中表达较低。肿瘤坏死因子（TNF）-α诱导蛋白8（TNFAIP8/TIPE）在CRC中高表达，并促进CRC的增殖、迁移和血管生成。然而，miR-539与TIPE之间的关系以及它们调节CRC增殖的机制仍有待探索。我们旨在研究miR-539在CRC增殖中的功能和机制。在功能上，miR-539可以结合并调节TIPE的表达，并且miR-539激活SAPK/JNK以下调谷胱甘肽过氧化物酶4（GPX4）的表达并促进铁死亡。我们的数据揭示了miR-539通过激活SAPK/JNK轴在调节CRC铁死亡中的新作用，为CRC异常增殖的机制提供了新的见解，并为晚期CRC提供了新的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc24/8487425/fe556b0407e2/41420_2021_659_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc24/8487425/7c67b5a9b9a4/41420_2021_659_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc24/8487425/e058284656ed/41420_2021_659_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc24/8487425/c6cc590b0928/41420_2021_659_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc24/8487425/064b164828c3/41420_2021_659_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc24/8487425/67052fbbe381/41420_2021_659_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc24/8487425/fe556b0407e2/41420_2021_659_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc24/8487425/7c67b5a9b9a4/41420_2021_659_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc24/8487425/e058284656ed/41420_2021_659_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc24/8487425/c6cc590b0928/41420_2021_659_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc24/8487425/064b164828c3/41420_2021_659_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc24/8487425/67052fbbe381/41420_2021_659_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc24/8487425/fe556b0407e2/41420_2021_659_Fig6_HTML.jpg

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