ING5, a Class II tumor suppressor, belongs to the inhibitor of growth (ING) candidate tumor suppressor family. It contains nuclear localization signal, plant homeodomain, novel conserved region, and leucine zipper-like domains. ING5 is involved in multiple cellular functions such as cell cycle regulation, apoptosis, and chromatin remodelling. It targets histone acetyltransferase or histone deacetylase complexes for local chromatin remodeling and is associated with pathways like EGFR/PI3K/Akt, IL-6/STAT3, Akt/NF-κB/NF-κB/MMP-9, IL-6/CXCL12, and Wnt/β-catenin, playing a crucial role in carcinogenesis [1,2,3,4,5].

In gastric carcinogenesis, ING5 abrogation in gastric stem-like and pdx1-positive cells causes gastric dysplasia and cancer, and conditional ING5 knockout in pdx1-positive and gastric chief cells increases MNU-induced gastric carcinogenesis [1,3]. In intestinal carcinogenesis, ING5 deletion increases AOM/DSS-induced colorectal carcinogenesis [1]. These KO and CKO mouse models demonstrate that ING5 has a suppressive effect on gastric and colorectal cancer development.

In conclusion, ING5 is essential in regulating various cellular functions and its loss-of-function in mouse models reveals its significance in suppressing carcinogenesis, especially in gastric and colorectal cancers. The study of ING5 provides insights into the mechanisms of cancer development, potentially offering new targets for cancer treatment [1,3].

References:

1. Zheng, Hua-Chuan, Xue, Hang, Jiang, Hua-Mao. 2022. The roles of ING5 in cancer: A tumor suppressor. In Frontiers in cell and developmental biology, 10, 1012179. doi:10.3389/fcell.2022.1012179. https://pubmed.ncbi.nlm.nih.gov/36425530/

2. Yang, Jiong, Liu, Xinli, Sun, Yang, Zhang, Feng, Zhang, Tao. . ING5 overexpression upregulates miR-34c-5p/Snail1 to inhibit EMT and invasion of lung cancer cells. In Acta biochimica et biophysica Sinica, 55, 809-817. doi:10.3724/abbs.2023074. https://pubmed.ncbi.nlm.nih.gov/37249332/

3. Zheng, Hua-Chuan, Xue, Hang, Wu, Xin, Zhao, En-Hong, Cui, Zheng-Guo. 2022. Transcriptional Regulation of ING5 and its Suppressive Effects on Gastric Cancer. In Frontiers in oncology, 12, 918954. doi:10.3389/fonc.2022.918954. https://pubmed.ncbi.nlm.nih.gov/35747809/

4. Wang, Yali, Tan, Jiao, Li, Jing, Chen, Huihui, Wang, Wei. . ING5 Inhibits Migration and Invasion of Esophageal Cancer Cells by Downregulating the IL-6/CXCL12 Signaling Pathway. In Technology in cancer research & treatment, 20, 15330338211039940. doi:10.1177/15330338211039940. https://pubmed.ncbi.nlm.nih.gov/34520285/

5. Liu, Xin-Li, Meng, Jin, Zhang, Xu-Tao, Zhao, Guan-Ren, Zhang, Tao. 2019. ING5 inhibits lung cancer invasion and epithelial-mesenchymal transition by inhibiting the WNT/β-catenin pathway. In Thoracic cancer, 10, 848-855. doi:10.1111/1759-7714.13013. https://pubmed.ncbi.nlm.nih.gov/30810286/