SOX15 transcriptionally increases the function of AOC1 to modulate ferroptosis and progression in prostate cancer

Abstract Amine oxidase copper-containing 1 (AOC1) is considered an oncogene in many types of tumors. Nevertheless, there have been no investigations of AOC1 and its regulatory mechanism in prostate cancer. Here, we reveal a novel action of AOC1 and a tumor suppressor mechanism in prostate cancer. AO...

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Main Authors: Yinghui Ding, Yuankang Feng, Zhenlin Huang, Yu Zhang, Xiang Li, Ruoyang Liu, Hao Li, Tao Wang, Yafei Ding, Zhankui Jia, Jinjian Yang
Format: Article
Language:English
Published: Nature Publishing Group 2022-08-01
Series:Cell Death and Disease
Online Access:https://doi.org/10.1038/s41419-022-05108-w
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author Yinghui Ding
Yuankang Feng
Zhenlin Huang
Yu Zhang
Xiang Li
Ruoyang Liu
Hao Li
Tao Wang
Yafei Ding
Zhankui Jia
Jinjian Yang
author_facet Yinghui Ding
Yuankang Feng
Zhenlin Huang
Yu Zhang
Xiang Li
Ruoyang Liu
Hao Li
Tao Wang
Yafei Ding
Zhankui Jia
Jinjian Yang
author_sort Yinghui Ding
collection DOAJ
description Abstract Amine oxidase copper-containing 1 (AOC1) is considered an oncogene in many types of tumors. Nevertheless, there have been no investigations of AOC1 and its regulatory mechanism in prostate cancer. Here, we reveal a novel action of AOC1 and a tumor suppressor mechanism in prostate cancer. AOC1 is downregulated in prostate cancer. Abatement of AOC1 in prostate cancer tissue is positively correlated with the tumor size, lymph node metastasis, and Gleason score for prostate cancer. Conversely, high expression of AOC1 is significantly associated with reduced proliferation and migration in prostate cancer both in vitro and in vivo. We show that the anticancer effect of AOC1 is mediated by its action on spermidine which leads to the activation of reactive oxygen species and ferroptosis. AOC1 expression in prostate cancer is positively regulated by the transcription factor SOX15. Therefore, SOX15 can transcriptionally promote AOC1 expression and strengthen this effect. Targeting AOC1 and SOX15 may be promising for the treatment of prostate cancer.
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spelling doaj.art-aa38089dd18b45979ab0d666e02055072022-12-22T02:48:42ZengNature Publishing GroupCell Death and Disease2041-48892022-08-0113811310.1038/s41419-022-05108-wSOX15 transcriptionally increases the function of AOC1 to modulate ferroptosis and progression in prostate cancerYinghui Ding0Yuankang Feng1Zhenlin Huang2Yu Zhang3Xiang Li4Ruoyang Liu5Hao Li6Tao Wang7Yafei Ding8Zhankui Jia9Jinjian Yang10Department of Urology, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Urology, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Urology, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Urology, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Urology, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Urology, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Urology, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Urology, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Urology, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Urology, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Urology, the First Affiliated Hospital of Zhengzhou UniversityAbstract Amine oxidase copper-containing 1 (AOC1) is considered an oncogene in many types of tumors. Nevertheless, there have been no investigations of AOC1 and its regulatory mechanism in prostate cancer. Here, we reveal a novel action of AOC1 and a tumor suppressor mechanism in prostate cancer. AOC1 is downregulated in prostate cancer. Abatement of AOC1 in prostate cancer tissue is positively correlated with the tumor size, lymph node metastasis, and Gleason score for prostate cancer. Conversely, high expression of AOC1 is significantly associated with reduced proliferation and migration in prostate cancer both in vitro and in vivo. We show that the anticancer effect of AOC1 is mediated by its action on spermidine which leads to the activation of reactive oxygen species and ferroptosis. AOC1 expression in prostate cancer is positively regulated by the transcription factor SOX15. Therefore, SOX15 can transcriptionally promote AOC1 expression and strengthen this effect. Targeting AOC1 and SOX15 may be promising for the treatment of prostate cancer.https://doi.org/10.1038/s41419-022-05108-w
spellingShingle Yinghui Ding
Yuankang Feng
Zhenlin Huang
Yu Zhang
Xiang Li
Ruoyang Liu
Hao Li
Tao Wang
Yafei Ding
Zhankui Jia
Jinjian Yang
SOX15 transcriptionally increases the function of AOC1 to modulate ferroptosis and progression in prostate cancer
Cell Death and Disease
title SOX15 transcriptionally increases the function of AOC1 to modulate ferroptosis and progression in prostate cancer
title_full SOX15 transcriptionally increases the function of AOC1 to modulate ferroptosis and progression in prostate cancer
title_fullStr SOX15 transcriptionally increases the function of AOC1 to modulate ferroptosis and progression in prostate cancer
title_full_unstemmed SOX15 transcriptionally increases the function of AOC1 to modulate ferroptosis and progression in prostate cancer
title_short SOX15 transcriptionally increases the function of AOC1 to modulate ferroptosis and progression in prostate cancer
title_sort sox15 transcriptionally increases the function of aoc1 to modulate ferroptosis and progression in prostate cancer
url https://doi.org/10.1038/s41419-022-05108-w
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