Tada1-KO Mouse

Tada1, also known as Hfi1 in Cryptococcus neoformans, is a gene encoding a protein that forms the core module of the Spt-Ada-Gcn Acetyltransferase (SAGA) complex, which is crucial for maintaining complex structural integrity [5]. It has significant biological importance as it may be involved in various biological processes and diseases.

In wheat, TaDA1 (a form of Tada1) was cloned and characterized as a conserved negative regulator of kernel size. Overexpression of TaDA1 decreased kernel size and weight, while its down-regulation had the opposite effect. TaDA1-A physically interacts with TaGW2-B, and they have additive effects on kernel weight [2]. In human cells, Tada1 was identified as a candidate gene in multiple studies. In a melanoma model, it was found through genome-scale CRISPR-Cas9 knockout screening as a gene whose loss is involved in resistance to vemurafenib [1]. In ovarian cancer cell lines, Tada1 was screened out as a novel gene potentially involved in cisplatin resistance using the whole human Genome-scale CRISPR-Cas9 knockout library [6]. Also, in human colorectal cancer cells, miR-7702 acts as a tumor suppressor by directly inhibiting Tada1, suppressing cell migration and invasion [3]. In lung squamous cell carcinoma, LINC00511 promotes tumor progression partially through up-regulating Tada1 via targeting miR-150-5p [4].

In conclusion, Tada1 plays diverse roles in different organisms and disease contexts. In plants, it regulates kernel size, while in human cancers, it is associated with drug resistance and cell migration/invasion. These findings from various model-based research, especially the use of genetic screening methods like CRISPR-Cas9, help to understand the biological functions of Tada1 and its potential as a therapeutic target in cancer treatment [1,2,3,4,6].

References:

1. Shalem, Ophir, Sanjana, Neville E, Hartenian, Ella, Doench, John G, Zhang, Feng. 2013. Genome-scale CRISPR-Cas9 knockout screening in human cells. In Science (New York, N.Y.), 343, 84-87. doi:10.1126/science.1247005. https://pubmed.ncbi.nlm.nih.gov/24336571/

2. Liu, Hong, Li, Huifang, Hao, Chenyang, Li, Tian, Zhang, Xueyong. 2019. TaDA1, a conserved negative regulator of kernel size, has an additive effect with TaGW2 in common wheat (Triticum aestivum L.). In Plant biotechnology journal, 18, 1330-1342. doi:10.1111/pbi.13298. https://pubmed.ncbi.nlm.nih.gov/31733093/

3. Liu, Han, Li, Dongdong, Fang, Hua, Ning, Junnan. 2018. Species-specific function of microRNA-7702 in human colorectal cancer cells via targeting TADA1. In American journal of translational research, 10, 2579-2589. doi:. https://pubmed.ncbi.nlm.nih.gov/30210694/

4. Wu, Ying, Li, Li, Wang, Qun, Wang, Xihua, Liu, Hongbing. . LINC00511 promotes lung squamous cell carcinoma proliferation and migration via inhibiting miR-150-5p and activating TADA1. In Translational lung cancer research, 9, 1138-1148. doi:10.21037/tlcr-19-701. https://pubmed.ncbi.nlm.nih.gov/32953492/

5. Yu, Chendi K, Stephenson, Christina J, Villamor, Tristan C, Schulz, Benjamin L, Fraser, James A. 2023. SAGA Complex Subunit Hfi1 Is Important in the Stress Response and Pathogenesis of Cryptococcus neoformans. In Journal of fungi (Basel, Switzerland), 9, . doi:10.3390/jof9121198. https://pubmed.ncbi.nlm.nih.gov/38132798/

6. Ouyang, Qianying, Liu, Yujie, Tan, Jieqiong, Zhou, Honghao, Liu, Yingzi. 2019. Loss of ZNF587B and SULF1 contributed to cisplatin resistance in ovarian cancer cell lines based on Genome-scale CRISPR/Cas9 screening. In American journal of cancer research, 9, 988-998. doi:. https://pubmed.ncbi.nlm.nih.gov/31218106/