Mier2, also known as Mesoderm induction early response 2, is a gene encoding an ELM2-SANT containing protein. It has been implicated in transcriptional regulation as it can recruit histone deacetylases (HDACs), specifically HDAC1 and HDAC2 in a cell-line dependent manner [3]. This recruitment is through its ELM2 domain, and the residue 228W in this domain is critical for HDAC recruitment. The gene is also associated with lipid metabolism-related pathways and has significance in tumor-related biological processes.

In renal cell carcinoma (RCC), Mier2 was identified as a novel biomarker. It promotes malignancy and sunitinib resistance by influencing lipid metabolism. Mechanistically, Mier2 binds to HDAC1, facilitating P53 deacetylation. Deacetylation of P53 hinders the transcriptional process of PGC1A, leading to intracellular lipid accumulation in RCC. Inhibiting the MIER2/HDAC1/P53/PGC1A pathway with Trichostatin A (TSA) may benefit sunitinib-resistant RCC patients [1]. In osteosarcoma, the circRNA hsa_circ_0002005 derived from the MIER2 gene is overexpressed. Knockdown of hsa_circ_0002005 reduces cell proliferation, migration, invasion, and metastatic potential, influencing proteins associated with epithelial-mesenchymal transition (EMT) [4]. Additionally, the small molecule UM171 can trigger Cul3-KBTBD4-mediated degradation of MIER2 through its ELM2 domain [2].

In conclusion, Mier2 plays essential roles in transcriptional regulation, lipid metabolism, and tumor-related processes such as drug resistance in RCC and cell behavior in osteosarcoma. These functions are revealed through various in-vitro and in-vivo studies. Understanding Mier2 is crucial for further exploring the mechanisms of tumorigenesis and developing potential therapeutic strategies for related cancers.

References:

1. Wei, Zhihao, Ye, Yuzhong, Liu, Chenchen, Cheng, Gong, Zhang, Xiaoping. 2024. MIER2/PGC1A elicits sunitinib resistance via lipid metabolism in renal cell carcinoma. In Journal of advanced research, 70, 287-305. doi:10.1016/j.jare.2024.04.032. https://pubmed.ncbi.nlm.nih.gov/38702028/

2. Žemaitis, Kristijonas, Ghosh, Sudip, Hansson, Jenny, Subramaniam, Agatheeswaran. 2023. The stem cell-supporting small molecule UM171 triggers Cul3-KBTBD4-mediated degradation of ELM2 domain-harboring proteins. In The Journal of biological chemistry, 299, 104662. doi:10.1016/j.jbc.2023.104662. https://pubmed.ncbi.nlm.nih.gov/36997086/

3. Derwish, Roya, Paterno, Gary D, Gillespie, Laura L. 2017. Differential HDAC1 and 2 Recruitment by Members of the MIER Family. In PloS one, 12, e0169338. doi:10.1371/journal.pone.0169338. https://pubmed.ncbi.nlm.nih.gov/28046085/

4. Yang, Junxu, Hu, Zizhu, Ru, Xiao, Huang, Hanji, Wei, Qingjun. 2025. Hsa_circ_0002005 aggravates osteosarcoma by increasing cell proliferation, migration, and invasion. In Gene, 942, 149221. doi:10.1016/j.gene.2025.149221. https://pubmed.ncbi.nlm.nih.gov/39761802/