Rmnd5a, short for Required for meiotic nuclear division 5 homolog A, functions as an E3 ubiquitin ligase. It is a member of the CTLH (carboxy-terminal to LisH) complex, which has E3-ligase enzymatic activity and is involved in fundamental biological processes such as proliferation, survival, programmed cell death, cell adhesion, and migration. The CTLH complex also interacts with key signaling pathways like PI3-kinase, WNT, TGFβ, and NFκB [2,4].

In pancreatic adenocarcinoma (PAAD), Rmnd5a is highly expressed and associated with overall survival. Overexpression of Rmnd5a significantly increases cell migration in PAAD cell lines. In contrast, overexpression of miR-590-5p, which targets Rmnd5a, downregulates its expression and decreases cell migratory ability [1].

In oral squamous cell carcinoma (OSCC), overexpression of Rmnd5A in human umbilical vein endothelial cells (HUVECs) reduces their proliferation, migration, and tube formation ability by inhibiting the activation of ERK and NF-κB pathway. OSCC cells can inhibit Rmnd5a expression of endothelial cells via exosomal miR-21 [3].

In breast cancer, abnormal expression levels of Rmnd5a are associated with a poor prognosis [5].

In conclusion, Rmnd5a, as an E3 ubiquitin ligase, plays important roles in multiple biological processes and is significantly involved in diseases such as pancreatic adenocarcinoma, oral squamous cell carcinoma, and breast cancer. The study of Rmnd5a provides insights into the mechanisms of these diseases and may offer potential therapeutic targets. [1,3,5]

References:

1. Chen, Sixing, Chen, Yu, Wen, Yao, Wu, Xiushan, Wang, Yuequn. 2021. miR-590-5p targets RMND5A and promotes migration in pancreatic adenocarcinoma cell lines. In Oncology letters, 22, 532. doi:10.3892/ol.2021.12793. https://pubmed.ncbi.nlm.nih.gov/34079591/

2. Huffman, Nickelas, Palmieri, Dario, Coppola, Vincenzo. 2019. The CTLH Complex in Cancer Cell Plasticity. In Journal of oncology, 2019, 4216750. doi:10.1155/2019/4216750. https://pubmed.ncbi.nlm.nih.gov/31885576/

3. Sun, Yu-Qi, Wang, Bing, Zheng, Lin-Wei, Zhao, Ji-Hong, Ren, Jian-Gang. 2024. Oral cancer cell to endothelial cell communication via exosomal miR-21/RMND5A pathway. In BMC oral health, 24, 82. doi:10.1186/s12903-024-03852-3. https://pubmed.ncbi.nlm.nih.gov/38229133/

4. Maitland, Matthew E R, Onea, Gabriel, Chiasson, Christopher A, Shaw, Gary S, Schild-Poulter, Caroline. 2019. The mammalian CTLH complex is an E3 ubiquitin ligase that targets its subunit muskelin for degradation. In Scientific reports, 9, 9864. doi:10.1038/s41598-019-46279-5. https://pubmed.ncbi.nlm.nih.gov/31285494/

5. Liu, Huijuan, Ye, Hui. 2017. Screening of the prognostic targets for breast cancer based co-expression modules analysis. In Molecular medicine reports, 16, 4038-4044. doi:10.3892/mmr.2017.7063. https://pubmed.ncbi.nlm.nih.gov/28731166/