Hoxa10, a member of the HOX gene family, is essential for embryonic development and has a significant impact on various biological processes and diseases. It is involved in pathways such as TGFB2/Smad/METTL3 in gastric cancer metastasis, and is also associated with uterine biogenesis, endometrial receptivity, embryo implantation, and stromal cell decidualization [1,2]. Genetic models like knockout (KO) or conditional knockout (CKO) mouse models are valuable for studying Hoxa10's functions.

In gastric cancer, Hoxa10 promotes metastasis by mediating epithelial-mesenchymal transition (EMT) via the TGFB2/Smad/METTL3 signaling axis [1]. In endometrial pathologies, down-regulation of Hoxa10, caused by genetic changes, methylation, miRNAs, endocrine disruptors, or organic pollutants, leads to endometrial epithelial cell proliferation, failure of stromal cell decidualization, and altered gene expression in cell cycle regulation, immunomodulation, and signaling pathways [2]. In endometriosis, high Hoxa10 DNA methylation level is observed in endometrial tissue, and its expression is generally down-regulated [3,5]. In articular chondrocytes, Hoxa10 promotes Gdf5 expression, which is important for joint development and homeostasis [4]. In prostate cancer, Hoxa10 expression is inversely associated with tumor differentiation and high expression is related to improved biochemical recurrence-free survival [6]. In endometrial stromal cells, Hoxa10 regulates cholesterol synthesis [7], and in the endometrium, it improves endometrial receptivity by up-regulating E-cadherin [8].

In conclusion, Hoxa10 plays crucial roles in embryonic development, especially in uterine-related processes such as endometrial receptivity and decidualization. Its dysregulation is associated with various diseases including gastric cancer, endometrial disorders, endometriosis, and prostate cancer. Studies using KO or CKO mouse models have been instrumental in uncovering these functions and disease associations, providing insights into potential therapeutic targets for these diseases.

References:

1. Song, Chenlong, Zhou, Chongzhi. 2021. HOXA10 mediates epithelial-mesenchymal transition to promote gastric cancer metastasis partly via modulation of TGFB2/Smad/METTL3 signaling axis. In Journal of experimental & clinical cancer research : CR, 40, 62. doi:10.1186/s13046-021-01859-0. https://pubmed.ncbi.nlm.nih.gov/33563300/

2. Mishra, Anuradha, Modi, Deepak. 2024. Role of HOXA10 in pathologies of the endometrium. In Reviews in endocrine & metabolic disorders, 26, 81-96. doi:10.1007/s11154-024-09923-8. https://pubmed.ncbi.nlm.nih.gov/39499452/

3. Elias, Marjanu Hikmah, Lazim, Nurunnajah, Sutaji, Zulazmi, Mokhtar, Mohd Helmy, Ahmad, Mohd Faizal. 2023. HOXA10 DNA Methylation Level in the Endometrium Women with Endometriosis: A Systematic Review. In Biology, 12, . doi:10.3390/biology12030474. https://pubmed.ncbi.nlm.nih.gov/36979165/

4. Murakami, Tomohiko, Ruengsinpinya, Lerdluck, Takahata, Yoshifumi, Hata, Kenji, Nishimura, Riko. 2023. HOXA10 promotes Gdf5 expression in articular chondrocytes. In Scientific reports, 13, 22778. doi:10.1038/s41598-023-50318-7. https://pubmed.ncbi.nlm.nih.gov/38123662/

5. Lazim, Nurunnajah, Elias, Marjanu Hikmah, Sutaji, Zulazmi, Mokhtar, Mohd Helmy, Ahmad, Mohd Faizal. 2023. Expression of HOXA10 Gene in Women with Endometriosis: A Systematic Review. In International journal of molecular sciences, 24, . doi:10.3390/ijms241612869. https://pubmed.ncbi.nlm.nih.gov/37629050/

6. Hatanaka, Yuji, de Velasco, Marco A, Oki, Takashi, Nishio, Kazuto, Uemura, Hirotsugu. 2019. HOXA10 expression profiling in prostate cancer. In The Prostate, 79, 554-563. doi:10.1002/pros.23761. https://pubmed.ncbi.nlm.nih.gov/30614022/

7. Yu, Meixing, Tang, Jia, Huang, Yanqing, Li, Ning, Quan, Qingli. 2022. HOXA10 Regulates the Synthesis of Cholesterol in Endometrial Stromal Cells. In Frontiers in endocrinology, 13, 852671. doi:10.3389/fendo.2022.852671. https://pubmed.ncbi.nlm.nih.gov/35546998/

8. Bi, Yin, Huang, Weiyu, Yuan, Lifang, Liu, Bo, Yang, Yihua. . HOXA10 improves endometrial receptivity by upregulating E-cadherin†. In Biology of reproduction, 106, 992-999. doi:10.1093/biolre/ioac007. https://pubmed.ncbi.nlm.nih.gov/35044439/