Hoxa10, belonging to the HOX gene family, is crucial for embryonic development. It acts as a transcription factor involved in various biological processes. In uterine development, it is essential for uterine biogenesis, endometrial receptivity, embryo implantation, and stromal cell decidualization. It also plays roles in cell cycle regulation and local immunomodulation [2,6].

In endometriosis, high HOXA10 DNA methylation level is observed in endometrium tissue, and its expression is often downregulated, which may be related to infertility [3,5]. In gastric cancer, HOXA10 is upregulated, especially in patients with lymph node metastasis. It promotes metastasis through mediating epithelial-mesenchymal transition, enriching in the TGFB2 promoter region, activating TGFβ/Smad signaling, and increasing m6A level and METTL3 expression [1]. In prostate cancer, HOXA10 expression is inversely associated with tumor differentiation, and high expression is linked to improved biochemical recurrence-free survival, suggesting a tumor-suppressive role [7]. In endometrial stromal cells, HOXA10 regulates cholesterol synthesis-related genes like HMGCR, MSMO1, ACAT2, HMGCS1, EBP, and SQLE [8]. Also, it improves endometrial receptivity by upregulating E-cadherin [9]. In articular chondrocytes, HOXA10 promotes the expression of Gdf5, a key gene in joint development and homeostasis [4].

In summary, Hoxa10 has diverse and essential functions in embryonic development, especially in uterine-related processes. Its dysregulation is associated with multiple diseases such as endometriosis, gastric cancer, and prostate cancer. Studies, including those using in vivo mouse models in some cases, have provided insights into its role in these biological processes and disease conditions, which may contribute to understanding disease mechanisms and developing potential treatments.

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. Modi, Deepak, Godbole, Geeta. 2009. HOXA10 signals on the highway through pregnancy. In Journal of reproductive immunology, 83, 72-8. doi:10.1016/j.jri.2009.07.009. https://pubmed.ncbi.nlm.nih.gov/19854516/

7. 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/

8. 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/

9. 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/