Dmrta1, or doublesex and mab-3-related transcription factor-like family A1, is a transcription factor involved in various biological processes. It plays a role in neural development, such as in the mammalian telencephalon where it may be regulated by Pax6 and is involved in the balance of cell proliferation and neuronal differentiation by regulating proneural gene expression [2]. It is also associated with otic development as Sf3b4 knockdown in Xenopus embryos led to reduced dmrta1 expression and affected otic development [5].

In esophageal squamous cell carcinoma (ESCC), knockdown of Dmrta1 decreased the proliferation rate of esophageal squamous carcinoma cells, increased cisplatin sensitivity, and decreased immune escape. Mechanistically, Dmrta1 forms a positive-feedback loop with SOX2 by binding to the promoter of SOX2, promoting ESCC progression and chemoresistance [1]. In dental fear and anxiety, a genome-wide association study found a significant association between a genetic locus near Dmrta1 and dental fear and anxiety sub-scales [3]. Also, in pan-cancer in silico analysis, deletion of Dmrta1 in the chr9p22.1-21.3 locus was associated with poor survival and increased hazard ratio in sarcoma datasets [4].

In conclusion, Dmrta1 is crucial in neural and otic development. Its role in disease, especially in ESCC where it impacts chemotherapy resistance and immune escape, highlights its potential as a therapeutic target. The association with dental fear and anxiety and cancer survival further emphasizes its importance in understanding the genetic basis of these conditions.

References:

1. Zhang, Rui, Zhou, Peng, Ou, Xia, Xi, Mian, Qing, Chen. 2023. The DMRTA1-SOX2 positive feedback loop promotes progression and chemotherapy resistance of esophageal squamous cell carcinoma. In Oncology research, 31, 887-897. doi:10.32604/or.2023.030184. https://pubmed.ncbi.nlm.nih.gov/37744275/

2. Kikkawa, Takako, Obayashi, Takeshi, Takahashi, Masanori, Numayama-Tsuruta, Keiko, Osumi, Noriko. 2013. Dmrta1 regulates proneural gene expression downstream of Pax6 in the mammalian telencephalon. In Genes to cells : devoted to molecular & cellular mechanisms, 18, 636-49. doi:10.1111/gtc.12061. https://pubmed.ncbi.nlm.nih.gov/23679989/

3. Zhou, Y, McNeil, D W, Haworth, S, Marazita, M L, Shaffer, J R. 2022. Genome-wide Scan of Dental Fear and Anxiety Nominates Novel Genes. In Journal of dental research, 101, 1526-1536. doi:10.1177/00220345221105226. https://pubmed.ncbi.nlm.nih.gov/35771046/

4. Gonçalves, Paola G, Reis, Rui M, Bidinotto, Lucas T. . Significance of Chr9p22.1-p21.3 Deletion in Cancer Development: A Pan-cancer In Silico Analysis. In Anticancer research, 42, 5291-5304. doi:10.21873/anticanres.16036. https://pubmed.ncbi.nlm.nih.gov/36288884/

5. Maharana, Santosh Kumar, Saint-Jeannet, Jean-Pierre. 2021. Molecular mechanisms of hearing loss in Nager syndrome. In Developmental biology, 476, 200-208. doi:10.1016/j.ydbio.2021.04.002. https://pubmed.ncbi.nlm.nih.gov/33864777/