Hif1an, also known as hypoxia-inducible factor 1-alpha subunit suppressor, plays a crucial role in regulating hypoxia-inducible factor 1-alpha (HIF-1α) stability and transcriptional action [1]. HIF-1α is a key transcription factor in the response to changes in oxygen availability, and the Hif1an-mediated regulation is part of the oxygen-sensing HIF hydroxylase pathway [2]. This regulation is important for multiple biological processes such as development, metabolism, and inflammation.

In breast cancer, lower Hif1an expression was associated with poor prognosis, and higher expression was linked to better overall survival. Hif1an expression was also closely related to chemokines and immune cell infiltration, including various types of immune cells like neutrophils, macrophages, and T-cells [1]. In keloid formation, circSLC8A1 inhibits the growth, migration, and extracellular matrix deposition of human keloid fibroblasts by regulating the miR-181a-5p/HIF1AN pathway [3]. In cardiomyocytes, pinoresinol diglucoside ameliorates hypoxia/reperfusion-induced injury by regulating miR-142-3p and HIF1AN [4]. In choriocarcinoma, METTL3 promotes miR-21-5p maturation in an m6A-dependent manner, which degrades HIF1AN, activating the HIF1A/VEGF pathway and accelerating choriocarcinoma progression [5]. In hypertrophic scar formation, rynchopeterine inhibits the formation by regulating the miR-21/HIF1AN axis [6]. M2 macrophage-derived exosomes increase skin flap survival through the HIF1AN/HIF-1α/VEGFA control [7]. And miR-135-5p promotes osteoblast differentiation by targeting HIF1AN in MC3T3-E1 cells [8].

In conclusion, Hif1an is essential for regulating HIF-1α and is involved in multiple biological processes and disease conditions. Its dysregulation is associated with various diseases including cancers, keloids, hypertrophic scars, and ischemic heart-related injuries. Research on Hif1an helps to understand the underlying molecular mechanisms of these diseases and may provide potential therapeutic targets.

References:

1. Tang, Shasha, Liu, Dongyang, Fang, Yuan, Wang, Hui, Cai, Fengfeng. 2023. Low expression of HIF1AN accompanied by less immune infiltration is associated with poor prognosis in breast cancer. In Frontiers in oncology, 13, 1080910. doi:10.3389/fonc.2023.1080910. https://pubmed.ncbi.nlm.nih.gov/36816977/

2. Kaelin, William G, Ratcliffe, Peter J. . Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. In Molecular cell, 30, 393-402. doi:10.1016/j.molcel.2008.04.009. https://pubmed.ncbi.nlm.nih.gov/18498744/

3. Yuan, Xiaoye, Chen, Baiye, Wang, Xueming. 2022. CircSLC8A1 targets miR-181a-5p/HIF1AN pathway to inhibit the growth, migration and extracellular matrix deposition of human keloid fibroblasts. In Burns : journal of the International Society for Burn Injuries, 49, 622-632. doi:10.1016/j.burns.2022.04.009. https://pubmed.ncbi.nlm.nih.gov/35610079/

4. Wei, Yuan, Xiao, Liang, Yingying, Liu, Haichen, Wang. 2022. Pinoresinol diglucoside ameliorates H/R-induced injury of cardiomyocytes by regulating miR-142-3p and HIF1AN. In Journal of biochemical and molecular toxicology, 36, e23175. doi:10.1002/jbt.23175. https://pubmed.ncbi.nlm.nih.gov/35962614/

5. Ye, Kefan, Li, Lingchuan, Wu, Bao, Wang, Dongjie. 2022. METTL3 m6A-dependently promotes miR-21-5p maturation to accelerate choriocarcinoma progression via the HIF1AN-induced inactivation of the HIF1A/VEGF pathway. In Genes & genomics, 44, 1311-1322. doi:10.1007/s13258-022-01309-x. https://pubmed.ncbi.nlm.nih.gov/36074324/

6. Zhao, Wenbin, Ye, Jianzhou, Yang, Xuesong, Zhang, Qiongyu, Li, Jiaqi. 2024. Rynchopeterine inhibits the formation of hypertrophic scars by regulating the miR-21/HIF1AN axis. In Experimental cell research, 440, 114114. doi:10.1016/j.yexcr.2024.114114. https://pubmed.ncbi.nlm.nih.gov/38823472/

7. Luo, Gaojie, Zhou, Zekun, Cao, Zheming, Tang, Juyu, Qing, Liming. 2023. M2 macrophage-derived exosomes induce angiogenesis and increase skin flap survival through HIF1AN/HIF-1α/VEGFA control. In Archives of biochemistry and biophysics, 751, 109822. doi:10.1016/j.abb.2023.109822. https://pubmed.ncbi.nlm.nih.gov/38030054/

8. Yin, Nuo, Zhu, Longzhang, Ding, Liang, Xue, Feng, Xiao, Haijun. 2019. MiR-135-5p promotes osteoblast differentiation by targeting HIF1AN in MC3T3-E1 cells. In Cellular & molecular biology letters, 24, 51. doi:10.1186/s11658-019-0177-6. https://pubmed.ncbi.nlm.nih.gov/31410089/