Hmgb3, belonging to the HMGB protein group from the superfamily of nuclear proteins with high electrophoretic mobility, plays diverse roles. HMGB proteins are involved in DNA-related cellular processes such as repair, replication, recombination, and transcription, and can act as cytokines during infectious, inflammatory, and injury responses [2].

In various disease-related studies, in silicosis, macrophage-derived exosomal Hmgb3 promotes M1 macrophage polarization and recruitment, regulating silica-induced pulmonary inflammation via the STAT3/MAPK (ERK1/2 and p38)/NF-κB pathways [1]. In small cell lung cancer, Hmgb3 was identified as a prognostic biomarker, and its overexpression promotes cell migration through transcriptional regulation of cell-junction-related genes [3]. In ovarian cancer, Hmgb3 promotes PARP inhibitor resistance by interacting with PARP1 [4]. In breast cancer, Hmgb3 is highly expressed and promotes cancer progression, while miR-145-5p can target it to restrain cancer cell proliferation, migration, and invasion [5]. In uterine decidualization, Hmgb3 may direct the process through targeting Ptn [6]. In papillary thyroid cancer, Hmgb3 is overexpressed, and its translocation activates cytoplasmic TLR3 and transmembrane TREM1, promoting cancer progression [7]. In epithelial ovarian cancer, Hmgb3 promotes malignant phenotypes and stemness via the MAPK/ERK signaling pathway [8]. Additionally, Hmgb3 binds to and facilitates the repair of N2 -alkylguanine lesions in DNA [9].

In conclusion, Hmgb3 is crucial in multiple biological processes and disease conditions. Its functions range from promoting inflammation in silicosis, influencing cancer cell behaviors in various cancers, to regulating uterine decidualization and DNA repair. These findings from different disease-based studies enhance our understanding of Hmgb3's role, potentially providing new targets for disease treatment.

References:

1. Qin, Xiaofeng, Niu, Zhiyuan, Chen, Hui, Hu, Yongbin. 2024. Macrophage-derived exosomal HMGB3 regulates silica-induced pulmonary inflammation by promoting M1 macrophage polarization and recruitment. In Particle and fibre toxicology, 21, 12. doi:10.1186/s12989-024-00568-8. https://pubmed.ncbi.nlm.nih.gov/38454505/

2. Chikhirzhina, Elena, Tsimokha, Anna, Tomilin, Alexey N, Polyanichko, Alexander. 2024. Structure and Functions of HMGB3 Protein. In International journal of molecular sciences, 25, . doi:10.3390/ijms25147656. https://pubmed.ncbi.nlm.nih.gov/39062899/

3. Liu, Qian, Zhang, Jing, Guo, Chenchen, Zhou, Hu, Zhang, Peng. . Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies. In Cell, 187, 184-203.e28. doi:10.1016/j.cell.2023.12.004. https://pubmed.ncbi.nlm.nih.gov/38181741/

4. Ma, Hanlin, Qi, Gonghua, Han, Fang, Yuan, Cunzhong, Kong, Beihua. 2022. HMGB3 promotes PARP inhibitor resistance through interacting with PARP1 in ovarian cancer. In Cell death & disease, 13, 263. doi:10.1038/s41419-022-04670-7. https://pubmed.ncbi.nlm.nih.gov/35332131/

5. Hu, Yangying, Wu, Deqi, Huang, Rong, Shi, Zhijie. 2022. HMGB3 Targeted by miR-145-5p Impacts Proliferation, Migration, Invasion, and Apoptosis of Breast Cancer Cells. In Computational and mathematical methods in medicine, 2022, 1954099. doi:10.1155/2022/1954099. https://pubmed.ncbi.nlm.nih.gov/36404911/

6. Wang, Kai, Yin, Yun-Hou, Yang, Zhan-Qing, Guo, Bin, Yue, Zhan-Peng. 2018. Hmgb3 Induces the Differentiation of Uterine Stromal Cells Through Targeting Ptn. In Reproductive sciences (Thousand Oaks, Calif.), 26, 891-899. doi:10.1177/1933719118792098. https://pubmed.ncbi.nlm.nih.gov/30081728/

7. Zhao, Yang, Lv, Hong-Jun, Deng, Xue-Yang, Shi, Bing-Yin, Fu, Jiao. 2024. Translocated HMGB3 is involved in papillary thyroid cancer progression by activating cytoplasmic TLR3 and transmembrane TREM1. In Cell cycle (Georgetown, Tex.), 22, 2584-2601. doi:10.1080/15384101.2024.2302244. https://pubmed.ncbi.nlm.nih.gov/38197217/

8. Ma, Hanlin, Qi, Gonghua, Han, Fang, Peng, Jiali, Kong, Beihua. 2023. HMGB3 promotes the malignant phenotypes and stemness of epithelial ovarian cancer through the MAPK/ERK signaling pathway. In Cell communication and signaling : CCS, 21, 144. doi:10.1186/s12964-023-01172-7. https://pubmed.ncbi.nlm.nih.gov/37328851/

9. Zhao, Ting, He, Xiaomei, Liang, Xiaochen, Gao, Zi, Wang, Yinsheng. 2024. HMGB3 and SUB1 Bind to and Facilitate the Repair of N2-Alkylguanine Lesions in DNA. In Journal of the American Chemical Society, 146, 22553-22562. doi:10.1021/jacs.4c06680. https://pubmed.ncbi.nlm.nih.gov/39101269/