Hmox1-KO Mouse

Hmox1, also known as heme-oxygenase 1, is a critical stress-response gene. It catalyzes the multistep oxidation of heme. The Hmox1 pathway has anti-thrombotic and anti-inflammatory properties, and is involved in multiple biological processes such as the regulation of iron metabolism [3,8].

In cancer research, studies show that upregulation of Hmox1 can induce ferroptosis. For example, donafenib and GSK-J4 synergistically promote Hmox1 expression, increasing intracellular Fe2+ levels and leading to ferroptosis in liver cancer [1]. EF24 upregulates Hmox1 to suppress GPX4 expression, inducing ferroptosis in osteosarcoma cells [2]. Shikonin and cisplatin overcome cisplatin resistance in ovarian cancer by inducing ferroptosis via Hmox1-mediated Fe2+ accumulation [4]. In non-small cell lung cancer, lncRNA RGMB-AS1 inhibits Hmox1 ubiquitination, enhancing ferroptosis [6]. In glioblastoma, IFI16 activates Hmox1 transcription to attenuate ferroptosis and enhance radioresistance [9]. In lens epithelial cells, Hmox1 promotes ferroptosis induced by erastin through modulating Fe2+ production [10]. In vascular smooth muscle cells, histone acetyltransferase P300 deficiency promotes ferroptosis by activating the HIF-1α/Hmox1 axis [5]. Also, in proliferative diabetic retinopathy, Hmox1 expression is correlated with M2 macrophage infiltration and ferroptosis [7].

In conclusion, Hmox1 is crucial in stress-response and iron-related metabolic processes. Its role in promoting ferroptosis in various cancers and its association with diseases like proliferative diabetic retinopathy, as revealed through functional studies, highlight its potential as a therapeutic target. The understanding of Hmox1's functions in these disease conditions provides insights into possible treatment strategies.

References:

1. Zheng, Chenyang, Zhang, Bo, Li, Yunyun, Wang, Jiabei, Liu, Lianxin. 2023. Donafenib and GSK-J4 Synergistically Induce Ferroptosis in Liver Cancer by Upregulating HMOX1 Expression. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2206798. doi:10.1002/advs.202206798. https://pubmed.ncbi.nlm.nih.gov/37330650/

2. Lin, Haiyingjie, Chen, Xiaoting, Zhang, Chengyong, Lin, Shaoqiang, Jin, Dadi. 2021. EF24 induces ferroptosis in osteosarcoma cells through HMOX1. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 136, 111202. doi:10.1016/j.biopha.2020.111202. https://pubmed.ncbi.nlm.nih.gov/33453607/

3. Hamilton, Fergus W, Somers, Julia, Mitchell, Ruth E, Ghazal, Peter, Timpson, Nicholas J. 2022. HMOX1 genetic polymorphisms and outcomes in infectious disease: A systematic review. In PloS one, 17, e0267399. doi:10.1371/journal.pone.0267399. https://pubmed.ncbi.nlm.nih.gov/35551540/

4. Ni, Maowei, Zhou, Jie, Zhu, Zhihui, Zheng, Zhiguo, Zhao, Huajun. 2023. Shikonin and cisplatin synergistically overcome cisplatin resistance of ovarian cancer by inducing ferroptosis via upregulation of HMOX1 to promote Fe2+ accumulation. In Phytomedicine : international journal of phytotherapy and phytopharmacology, 112, 154701. doi:10.1016/j.phymed.2023.154701. https://pubmed.ncbi.nlm.nih.gov/36773431/

5. Shi, Juan, Wang, Qun-Hui, Wei, Xiang, Jiang, Ding-Sheng, Ma, Ming-Jia. 2023. Histone acetyltransferase P300 deficiency promotes ferroptosis of vascular smooth muscle cells by activating the HIF-1α/HMOX1 axis. In Molecular medicine (Cambridge, Mass.), 29, 91. doi:10.1186/s10020-023-00694-7. https://pubmed.ncbi.nlm.nih.gov/37415103/

6. Gao, Gui-Bin, Chen, Liang, Pan, Jia-Feng, Shan, Ge, Li, Jin. 2024. LncRNA RGMB-AS1 inhibits HMOX1 ubiquitination and NAA10 activation to induce ferroptosis in non-small cell lung cancer. In Cancer letters, 590, 216826. doi:10.1016/j.canlet.2024.216826. https://pubmed.ncbi.nlm.nih.gov/38574881/

7. Zhou, Haixiang, Zhang, Lusi, Ding, Chun, Zhou, Yedi, Li, Yun. 2024. Upregulation of HMOX1 associated with M2 macrophage infiltration and ferroptosis in proliferative diabetic retinopathy. In International immunopharmacology, 134, 112231. doi:10.1016/j.intimp.2024.112231. https://pubmed.ncbi.nlm.nih.gov/38739977/

8. Batra, Neelu, De Souza, Cristabelle, Batra, Jyoti, Raetz, Alan G, Yu, Ai-Ming. 2020. The HMOX1 Pathway as a Promising Target for the Treatment and Prevention of SARS-CoV-2 of 2019 (COVID-19). In International journal of molecular sciences, 21, . doi:10.3390/ijms21176412. https://pubmed.ncbi.nlm.nih.gov/32899231/

9. Zhou, Yuchuan, Zeng, Liang, Cai, Linbo, Zhang, Jianghong, Shao, Chunlin. 2025. Cellular senescence-associated gene IFI16 promotes HMOX1-dependent evasion of ferroptosis and radioresistance in glioblastoma. In Nature communications, 16, 1212. doi:10.1038/s41467-025-56456-y. https://pubmed.ncbi.nlm.nih.gov/39890789/

10. Liao, Shengjie, Huang, Mi, Liao, Yanli, Yuan, Chao. 2022. HMOX1 Promotes Ferroptosis Induced by Erastin in Lens Epithelial Cell through Modulates Fe2+ Production. In Current eye research, 48, 25-33. doi:10.1080/02713683.2022.2138450. https://pubmed.ncbi.nlm.nih.gov/36300537/