Ankrd46, or Ankyrin repeat domain 46, contains ankyrin repeat domains which are involved in protein-protein interactions. Although its exact core function is yet to be fully defined, it seems to be associated with multiple biological processes and diseases. Its role in different pathways might be revealed through further genetic model-based studies [1-9].

In breast cancer, the circ_PRDM5/miR-25-3p/ANKRD46 axis is associated with cell malignant behaviors. Circ_PRDM5 can upregulate ANKRD46 by targeting miR-25-3p, and overexpression of circ_PRDM5 suppresses BC cell proliferation and motility, while enhancing apoptosis [1]. In murine embryo implantation, miR-451 may play a major role by targeting Ankrd46 [3]. In post-menopausal osteoporosis, moderate-intensity treadmill exercise can affect bone mass, and ANKRD46 is one of the key proteins that could be the target of such exercise [2]. In alcohol use disorder, ANKRD46 was identified as a gene with ultra-rare non-synonymous variants and protein-truncating variants associated with loss-of-function [4]. In breast cancer, ANKRD46 is a direct target of miR-21, and knockdown of miR-21 increases ANKRD46 expression and inhibits breast cancer cell growth and migration [5]. In the co-pathogenesis of type 2 diabetes mellitus and mild cognitive dysfunction in the elderly, ANKRD46 is one of the hub genes [6]. In nasopharyngeal carcinoma cells, ANKRD46, located in the 8q21-qter region, is up-regulated in taxol-resistant sub-lines and may be related to cell adhesion and cell cycle [7]. In gastric cancer, ANKRD46 was concordantly deregulated by genomic aberrations [8]. In post-Chernobyl thyroid cancers, the expression of ANKRD46 in tumour tissue was significantly associated with iodine-131 dose [9].

In conclusion, Ankrd46 is involved in multiple biological processes and disease conditions, such as cancer, embryo implantation, and osteoporosis. Studies on Ankrd46 using different research models, though not specifically KO/CKO mouse models in the provided references, have provided insights into its role in these areas, highlighting its importance in understanding disease mechanisms and potentially developing new treatment strategies.

References:

1. Lu, Qin, Sun, Huihui, Yu, Qian, Tang, Dongdong. 2023. Circ_PRDM5/miR-25-3p/ANKRD46 axis is associated with cell malignant behaviors in subjects with breast cancer evaluated by ultrasound. In Journal of biochemical and molecular toxicology, 37, e23469. doi:10.1002/jbt.23469. https://pubmed.ncbi.nlm.nih.gov/37485755/

2. Yang, Yong-Jie, Li, Ye, Gao, Li. 2023. Postmenopausal osteoporosis: Effect of moderate-intensity treadmill exercise on bone proteomics in ovariectomized rats. In Frontiers in surgery, 9, 1000464. doi:10.3389/fsurg.2022.1000464. https://pubmed.ncbi.nlm.nih.gov/36684175/

3. Li, Zhengyu, Jia, Jia, Gou, Jinhai, Zhao, Xia, Yi, Tao. 2014. MicroRNA-451 plays a role in murine embryo implantation through targeting Ankrd46, as implicated by a microarray-based analysis. In Fertility and sterility, 103, 834-4.e4. doi:10.1016/j.fertnstert.2014.11.024. https://pubmed.ncbi.nlm.nih.gov/25542822/

4. Hill, Shirley Y, Hostyk, Joseph. 2023. A whole exome sequencing study to identify rare variants in multiplex families with alcohol use disorder. In Frontiers in psychiatry, 14, 1216493. doi:10.3389/fpsyt.2023.1216493. https://pubmed.ncbi.nlm.nih.gov/37915799/

5. Yan, Li Xu, Wu, Qi Nian, Zhang, Yan, Zeng, Yi Xin, Shao, Jian Yong. 2011. Knockdown of miR-21 in human breast cancer cell lines inhibits proliferation, in vitro migration and in vivo tumor growth. In Breast cancer research : BCR, 13, R2. doi:10.1186/bcr2803. https://pubmed.ncbi.nlm.nih.gov/21219636/

6. Zhang, Yu, Deng, Shengfeng, Zhong, Hongfei, Geng, Rulin, Tu, Qiuyun. 2023. Exploration and Clinical Verification of the Blood Co-Expression Genes of Type 2 Diabetes Mellitus and Mild Cognitive Dysfunction in the Elderly. In Biomedicines, 11, . doi:10.3390/biomedicines11040993. https://pubmed.ncbi.nlm.nih.gov/37189611/

7. Li, Wei, You, Yating, Zhang, Xiaowei, Qin, Jiangbo, Tan, Guolin. 2015. Amplification of chromosome 8q21-qter associated with the acquired paclitaxel resistance of nasopharyngeal carcinoma cells. In International journal of clinical and experimental pathology, 8, 12346-56. doi:. https://pubmed.ncbi.nlm.nih.gov/26722421/

8. Cheng, Lei, Wang, Ping, Yang, Sheng, Gao, Hengjun, Zhang, Qinghua. 2012. Identification of genes with a correlation between copy number and expression in gastric cancer. In BMC medical genomics, 5, 14. doi:10.1186/1755-8794-5-14. https://pubmed.ncbi.nlm.nih.gov/22559327/

9. Abend, M, Pfeiffer, R M, Ruf, C, Mabuchi, K, Brenner, A V. 2013. Iodine-131 dose-dependent gene expression: alterations in both normal and tumour thyroid tissues of post-Chernobyl thyroid cancers. In British journal of cancer, 109, 2286-94. doi:10.1038/bjc.2013.574. https://pubmed.ncbi.nlm.nih.gov/24045656/