Ttc22-KO Mouse

Ttc22, or tetratricopeptide repeat domain 22, is involved in multiple biological processes. It has been shown to be associated with RNA-related functions and cancer-related pathways. Mining of Genotype-Tissue Expression (GTEx) datasets indicates it is widely co-expressed with WTAP and FTO in many human tissues. Its function seems to be related to the regulation of m6A-mediated gene expression, which is an important epigenetic RNA modification involved in various biological processes such as gene expression regulation, cell differentiation, and development [1].

In colon cancer, Ttc22 promotes m6A-mediated WTAP expression and metastasis in an RPL4 binding-dependent pattern. It directly interacts with 60S ribosomal protein L4 (RPL4), enhancing the binding of WTAP mRNA to RPL4, as well as the stability and translation efficiency of WTAP mRNA, thus increasing WTAP protein levels. Ttc22 also triggers a positive feedback loop between WTAP expression and WTAP mRNA m6A modification, leading to an increased m6A level in total RNA. This upregulates the expression of SNAI1, promoting lung metastases of colon cancer cells in mice [1].

In pancreatic cancer, pan-cancer analysis and single-cell sequencing revealed differential expression of Ttc22. Clinical data showed a negative association between its expression and survival prognosis. Functional enrichment analysis validated its correlation with immune infiltration, and in vitro assays demonstrated its effect on the migration and invasion of pancreatic cancer cells, suggesting it could be a potential prognostic marker and therapeutic target [2].

In colon cancer, miR663a-TTC22V1 axis inhibits metastasis. TTC22V1 mRNA is a target of miR663a, and high TTC22V1 expression is a poor survival factor for colon cancer patients [3]. Additionally, integration of DNA sequencing and transcriptomic data found that Ttc22 is genome-wide significantly associated with low-density lipoprotein cholesterol in two UK10K whole genome sequencing cohorts [4].

In conclusion, Ttc22 is involved in multiple biological processes, with a significant impact on cancer-related functions such as metastasis and immune infiltration in colon and pancreatic cancer. Its role in lipid-related traits also indicates its broad biological importance. The findings from these studies, some of which likely involved in vivo models, contribute to understanding the biological functions of Ttc22 and offer potential directions for cancer treatment and lipid-related disease research.

References:

1. You, Abin, Tian, Wei, Yuan, Hongfan, Zhou, Jing, Deng, Dajun. 2022. TTC22 promotes m6A-mediated WTAP expression and colon cancer metastasis in an RPL4 binding-dependent pattern. In Oncogene, 41, 3925-3938. doi:10.1038/s41388-022-02402-x. https://pubmed.ncbi.nlm.nih.gov/35798874/

2. Ding, Yuntao, Wang, Huizhi, Cao, Wenyu, Zhou, Yujing, Xu, Min. 2023. TTC22 as a potential prognostic marker and therapeutic target in pancreatic cancer: Insights into immune infiltration and epithelial‑mesenchymal transition. In Oncology letters, 27, 11. doi:10.3892/ol.2023.14143. https://pubmed.ncbi.nlm.nih.gov/38034483/

3. Tian, Wei, Du, Yantao, Ma, Yuwan, Zhou, Jing, Deng, Dajun. 2019. miR663a‑TTC22V1 axis inhibits colon cancer metastasis. In Oncology reports, 41, 1718-1728. doi:10.3892/or.2019.6969. https://pubmed.ncbi.nlm.nih.gov/30664167/

4. Yang, Tianzhong, Wu, Chong, Wei, Peng, Pan, Wei. . Integrating DNA sequencing and transcriptomic data for association analyses of low-frequency variants and lipid traits. In Human molecular genetics, 29, 515-526. doi:10.1093/hmg/ddz314. https://pubmed.ncbi.nlm.nih.gov/31919517/