High Mobility Group A1 (HMGA1), a nonhistone chromatin structural protein with no transcriptional activity, mainly regulates genes by modifying DNA structure. It is involved in multiple pathways such as Wnt/β -catenin, PI3K/Akt, Hippo, and MEK/ERK. HMGA1 is rare in adult cells but increases in highly proliferative cells like embryos. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions [4].

In sepsis induced cardiomyopathy (SIC) mouse models, HMGA1 overexpression aggravated cardiac dysfunction, inflammation, and apoptosis, while its knockdown in H9c2 cardiomyocytes attenuated inflammation but aggravated apoptosis [1]. In pancreatic ductal adenocarcinomas (PDAC) models, HMGA1 deficiency disrupted oncogenic properties and tumor progression [2]. In esophageal squamous cell carcinoma (ESCC) models, inhibition of HMGA1 enhanced ferroptosis and restored sensitivity to cisplatin [3]. In colorectal cancer models, conditional knockout (Hmga1△IEC) and knock -in (Hmga1IEC-OE/+) mouse models showed that HMGA1 promoted CRC progression by upregulating fatty acid synthase (FASN) [5]. In ESCC mouse models, conditional knockout of HMGA1 reduced 4-nitroquinoline-1-oxide (4NQO)-induced esophageal tumorigenesis [6].

In conclusion, HMGA1 plays a crucial role in various biological processes and disease conditions. Model-based research, especially using KO/CKO mouse models, has revealed its significant contributions to diseases like SIC, PDAC, ESCC, and colorectal cancer, providing insights into potential therapeutic strategies targeting HMGA1 in these diseases.

References:

1. Cai, Zhu-Lan, Shen, Bo, Yuan, Yuan, Wu, Qing-Qing, Tang, Qi-Zhu. 2020. The effect of HMGA1 in LPS-induced Myocardial Inflammation. In International journal of biological sciences, 16, 1798-1810. doi:10.7150/ijbs.39947. https://pubmed.ncbi.nlm.nih.gov/32398950/

2. Chia, Lionel, Wang, Bowen, Kim, Jung-Hyun, Wood, Laura, Resar, Linda. 2023. HMGA1 induces FGF19 to drive pancreatic carcinogenesis and stroma formation. In The Journal of clinical investigation, 133, . doi:10.1172/JCI151601. https://pubmed.ncbi.nlm.nih.gov/36919699/

3. Yang, Jing-Yu, Lei, Xin-Yuan, He, Kai-Yue, Jian, Yong-Ping, Xu, Zhi-Xiang. 2024. HMGA1 drives chemoresistance in esophageal squamous cell carcinoma by suppressing ferroptosis. In Cell death & disease, 15, 158. doi:10.1038/s41419-024-06467-2. https://pubmed.ncbi.nlm.nih.gov/38383528/

4. Wang, Lu, Zhang, Ji, Xia, Min, Zu, Xuyu, Zhong, Jing. 2022. High Mobility Group A1 (HMGA1): Structure, Biological Function, and Therapeutic Potential. In International journal of biological sciences, 18, 4414-4431. doi:10.7150/ijbs.72952. https://pubmed.ncbi.nlm.nih.gov/35864955/

5. Zhao, Yuan, Liu, Meng-Jie, Zhang, Lei, Jian, Yong-Ping, Xu, Zhi-Xiang. 2024. High mobility group A1 (HMGA1) promotes the tumorigenesis of colorectal cancer by increasing lipid synthesis. In Nature communications, 15, 9909. doi:10.1038/s41467-024-54400-0. https://pubmed.ncbi.nlm.nih.gov/39548107/

6. Liu, Meng-Jie, Zhao, Yuan, Li, Qiu-Tong, Jian, Yong-Ping, Xu, Zhi-Xiang. 2024. HMGA1 promotes the progression of esophageal squamous cell carcinoma by elevating TKT-mediated upregulation of pentose phosphate pathway. In Cell death & disease, 15, 541. doi:10.1038/s41419-024-06933-x. https://pubmed.ncbi.nlm.nih.gov/39080260/