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Role of HMGA2: In adults, HMGA2 is usually expressed in limited amounts in kidney, liver, lung, and uterus. Rearrangements of HMGA2 resulting in its re-expression and upregulation have been detected in numerous human cancers as well as several benign mesenchymal tumors, including lipomas, uterine leiomyomas, pulmonary chondroid hamartomas, aggressive angiomyxomas, pleomorphic adenomas of salivary glands and fibroadenomas of breast.

HMGA2 promotes tumorigenesis by several mechanisms, including promoting cell cycle entry, inhibiting apoptosis, influencing DNA repair pathways, and promoting epithelial-to-mesenchymal transition via MAPK/ERK, TGFβ/Smad, PI3K/AKT/mTOR, NFκB, and STAT3 pathways. HMGA2 also renders cancer cells resistant to chemotherapeutic agents.

Image source: Mansoori B, Mohammadi A, Ditzel HJ, Duijf PHG, Khaze V, Gjerstorff MF, Baradaran B. HMGA2 as a Critical Regulator in Cancer Development. Genes. 2021; 12(2):269. https://doi.org/10.3390/genes12020269; used under Creative Commons Attribution (CC BY) license.

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