Wu Xiaohui, Bai Yuke, Zhu Jiahao, Yan Bing, Song Jingyi, Chen Liang
Hemoglobin (Hb) is traditionally recognized as an erythroid-specific protein with the core function of mediating transmembrane transport of oxygen and carbon dioxide. In recent years, emerging studies have confirmed that hemoglobin is also expressed in the cytoplasm of various normal somatic cells and tumor cells. In normal somatic cells such as alveolar epithelial cells, vascular endothelial cells and chondrocytes, hemoglobin exerts multiple biological functions including oxygen storage, protection of smooth muscle soluble guanylate cyclase from excessive desensitization to nitric oxide, as well as hypoxia resistance, blood pressure regulation and antioxidant effects. In most tumor cells, hemoglobin expression is abnormally upregulated, while a small number of cases show a downregulated trend. Its expression level is closely associated with malignant biological behaviors of tumor cells such as survival, radioresistance and distant metastasis, making it a potential biomarker for tumor diagnosis and prognostic evaluation. This paper systematically reviews the discovery process and functional research progress of hemoglobin in normal non-erythroid somatic cells and tumor cells, explores the feasibility of hemoglobin as a therapeutic target for related diseases, and provides new ideas and directions for the diagnosis and treatment of these diseases.