Hmox1, also known as heme-oxygenase 1, is a critical stress-response gene. It catalyzes the multistep oxidation of heme [3]. The Hmox1 pathway has anti-thrombotic and anti-inflammatory properties, and can inhibit platelet aggregation [9]. As a major intracellular Fe pools, heme could be metabolized into ferrous iron, carbon monoxide, and biliverdin by Hmox1, playing a role in iron metabolism [10].

In cancer research, multiple studies have shown the significance of Hmox1 in ferroptosis. Donafenib and GSK-J4 synergistically promote Hmox1 expression, increase intracellular Fe2+ level, and eventually lead to ferroptosis in liver cancer [1]. EF24 upregulates Hmox1 to suppress GPX4 expression, thereby inducing ferroptosis in osteosarcoma cells [2]. Shikonin and cisplatin overcome cisplatin resistance in ovarian cancer through ferroptosis by upregulating Hmox1 to promote Fe2+ accumulation [4]. P300 deficiency promotes ferroptosis of vascular smooth muscle cells by activating the HIF-1α/Hmox1 axis [5]. LncRNA RGMB-AS1 inhibits Hmox1 ubiquitination, leading to increased Hmox1 stability and enhanced ferroptosis in non-small cell lung cancer [6]. Hmox1 expression is also associated with M2 macrophage infiltration and ferroptosis in proliferative diabetic retinopathy [7]. In glioblastoma, IFI16 activates Hmox1 transcription to attenuate ferroptosis and enhance radioresistance [8]. In the lens epithelial cell, Hmox1 increases the susceptibility to erastin-induced ferroptosis [10].

In conclusion, Hmox1 is essential in stress-response and iron metabolism. Its role in promoting ferroptosis has been demonstrated in various cancer types and other disease conditions, such as proliferative diabetic retinopathy. The study of Hmox1 using different experimental models helps to understand its function in biological processes and disease mechanisms, providing potential therapeutic targets for related diseases.