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...
Main Authors: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1811315182871248896 |
---|---|
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. |
first_indexed | 2024-04-13T11:25:38Z |
format | Article |
id | doaj.art-aa38089dd18b45979ab0d666e0205507 |
institution | Directory Open Access Journal |
issn | 2041-4889 |
language | English |
last_indexed | 2024-04-13T11:25:38Z |
publishDate | 2022-08-01 |
publisher | Nature Publishing Group |
record_format | Article |
series | Cell Death and Disease |
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 |
work_keys_str_mv | AT yinghuiding sox15transcriptionallyincreasesthefunctionofaoc1tomodulateferroptosisandprogressioninprostatecancer AT yuankangfeng sox15transcriptionallyincreasesthefunctionofaoc1tomodulateferroptosisandprogressioninprostatecancer AT zhenlinhuang sox15transcriptionallyincreasesthefunctionofaoc1tomodulateferroptosisandprogressioninprostatecancer AT yuzhang sox15transcriptionallyincreasesthefunctionofaoc1tomodulateferroptosisandprogressioninprostatecancer AT xiangli sox15transcriptionallyincreasesthefunctionofaoc1tomodulateferroptosisandprogressioninprostatecancer AT ruoyangliu sox15transcriptionallyincreasesthefunctionofaoc1tomodulateferroptosisandprogressioninprostatecancer AT haoli sox15transcriptionallyincreasesthefunctionofaoc1tomodulateferroptosisandprogressioninprostatecancer AT taowang sox15transcriptionallyincreasesthefunctionofaoc1tomodulateferroptosisandprogressioninprostatecancer AT yafeiding sox15transcriptionallyincreasesthefunctionofaoc1tomodulateferroptosisandprogressioninprostatecancer AT zhankuijia sox15transcriptionallyincreasesthefunctionofaoc1tomodulateferroptosisandprogressioninprostatecancer AT jinjianyang sox15transcriptionallyincreasesthefunctionofaoc1tomodulateferroptosisandprogressioninprostatecancer |