ANKRD22, ankyrin repeat domain 22, is a nuclear-encoded mitochondrial membrane protein. It is highly expressed in normal gastric mucosal epithelial cells and activated macrophages. As a regulator of mitochondrial Ca2+, it is involved in the Wnt/β-catenin pathway, playing a significant role in the repair of gastric mucosal damage [1]. It also has implications in inflammation-related processes and is associated with various disease conditions.

ANKRD22-deficient mice are more susceptible to IMQ-induced psoriasiform inflammation. The deficiency leads to excessive activation of the TNFRII-NIK-mediated noncanonical NF-κB signaling pathway, resulting in hyperproduction of IL-23 in DCs [2]. In ovarian cancer, knockout of Ankrd22 in mouse CD11b+Ly6G+Ly6Clow cells increases the expression level of CCR2 and the immunosuppressive activity of PMN-MDSCs [3]. In septic ARDS model mice, knockdown of ANKRD22 significantly attenuates acute lung injury and reduces the M1 polarization of lung macrophages [4]. In glioma, loss of ANKRD22 suppresses glioma cell proliferation, migration, invasion and cell cycle progression in vitro and tumor growth in vivo [5]. In papillary thyroid carcinoma, knockdown of ANKRD22 reduces cell viability, colony formation, and cell invasion and migration abilities [6].

In conclusion, ANKRD22 is involved in multiple biological processes. Research using gene-knockout mouse models has revealed its significance in diseases such as gastric mucosal injury, psoriasis, ovarian cancer, septic ARDS, glioma, and papillary thyroid carcinoma. These findings provide potential therapeutic targets for these diseases.

References:

1. Wang, Rui, Wu, Youhe, Zhu, Yue, Yao, Sheng, Zhu, Yongliang. 2022. ANKRD22 is a novel therapeutic target for gastric mucosal injury. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 147, 112649. doi:10.1016/j.biopha.2022.112649. https://pubmed.ncbi.nlm.nih.gov/35051858/

2. Xia, Xichun, Zhu, Leqing, Xu, Miaomiao, Huang, Fang, Gao, Yunfei. 2024. ANKRD22 promotes resolution of psoriasiform skin inflammation by antagonizing NIK-mediated IL-23 production. In Molecular therapy : the journal of the American Society of Gene Therapy, 32, 1561-1577. doi:10.1016/j.ymthe.2024.03.007. https://pubmed.ncbi.nlm.nih.gov/38454607/

3. Chen, Huanhuan, Yang, Keqing, Pang, Lingxiao, Zhu, Yongliang, Zhou, Jianwei. . ANKRD22 is a potential novel target for reversing the immunosuppressive effects of PMN-MDSCs in ovarian cancer. In Journal for immunotherapy of cancer, 11, . doi:10.1136/jitc-2022-005527. https://pubmed.ncbi.nlm.nih.gov/36822671/

4. Zhang, Shi, Liu, Yao, Zhang, Xiao-Long, Sun, Yun, Lu, Zhong-Hua. 2023. ANKRD22 aggravates sepsis-induced ARDS and promotes pulmonary M1 macrophage polarization. In Journal of translational autoimmunity, 8, 100228. doi:10.1016/j.jtauto.2023.100228. https://pubmed.ncbi.nlm.nih.gov/38225946/

5. Liu, Xin, Zhao, Junling, Wu, Qiang, Lu, Wenpeng, Feng, Yan. . ANKRD22 promotes glioma proliferation, migration, invasion, and epithelial-mesenchymal transition by upregulating E2F1-mediated MELK expression. In Journal of neuropathology and experimental neurology, 82, 631-640. doi:10.1093/jnen/nlad034. https://pubmed.ncbi.nlm.nih.gov/37164633/

6. Wu, Yange, Chen, WenXiu, Zhang, Bo, Liu, HongXia. 2023. ANKRD22 knockdown suppresses papillary thyroid cell carcinoma growth and migration and modulates the Wnt/β-catenin signaling pathway. In Tissue & cell, 84, 102193. doi:10.1016/j.tice.2023.102193. https://pubmed.ncbi.nlm.nih.gov/37586180/