{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMEX3A is an RNA‐binding protein that plays a pivotal role in the regulation of stem cell dynamics. In the intestinal epithelium, MEX3A marks a slowly cycling subpopulation of Lgr5+ stem cells that serve as a reserve pool, contributing to tissue regeneration after cytotoxic insults. These cells, characterized by a unique expression program and lower proliferation gene levels, can replenish the rapidly dividing stem cell compartment during homeostasis and after chemotherapy or radiation, thereby safeguarding epithelial integrity. This function is underscored by mouse model studies in which loss of MEX3A disrupts epithelial turnover and organoid maturation via modulation of key pathways such as Wnt and PPAR signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the realm of cancer biology, heightened MEX3A levels have been implicated in tumor progression and therapy resistance. In pancreatic ductal adenocarcinoma, for example, upregulation of MEX3A correlates with advanced disease stage and chemoresistance through its ability to stabilize pro-proliferative transcripts such as cyclin‐dependent kinase 6, thus promoting cell cycle progression. Similarly, in colorectal cancer, the E2F3-MEX3A-KLF4 axis is critical in maintaining cancer cells in a proliferative and undifferentiated state, contributing to radioresistance and poorer patient prognosis. These findings highlight the dual role of MEX3A in sustaining stem cell features in normal tissue as well as hijacking these mechanisms in cancer to support malignancy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond the intestinal context, MEX3A exerts essential regulatory roles in other stem cell systems. In the adult murine neural stem cell niche, for instance, MEX3A modulates a specific repertoire of stemness-associated transcripts, ensuring that activated neural stem cells can return to quiescence and thereby maintain long-term self-renewal and proper neuronal differentiation. Moreover, emerging evidence in breast cancer further suggests that MEX3A contributes to tumor genesis and progression, although its detailed mechanistic contributions in this setting remain to be fully elucidated."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Francisco M Barriga, Elisa Montagni, Miyeko Mana, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mex3a Marks a Slowly Dividing Subpopulation of Lgr5+ Intestinal Stem Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Stem Cell (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.stem.2017.02.007"}], "href": "https://doi.org/10.1016/j.stem.2017.02.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28285904"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28285904"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Bruno Pereira, Ana L Amaral, Alexandre Dias, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MEX3A regulates Lgr5"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " stem cell maintenance in the developing intestinal epithelium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embr.201948938"}], "href": "https://doi.org/10.15252/embr.201948938"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32052574"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32052574"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Valentina Panzeri, Isabella Manni, Alessia Capone, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The RNA-binding protein MEX3A is a prognostic factor and regulator of resistance to gemcitabine in pancreatic ductal adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Oncol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1878-0261.12847"}], "href": "https://doi.org/10.1002/1878-0261.12847"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33159833"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33159833"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Haixia Li, Jinghui Liang, Jiang Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mex3a promotes oncogenesis through the RAP1/MAPK signaling pathway in colorectal cancer and is inhibited by hsa-miR-6887-3p."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Commun (Lond) (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cac2.12149"}], "href": "https://doi.org/10.1002/cac2.12149"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33638620"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33638620"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xu Yang, Guilin Li, Yuhua Tian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identifying the E2F3-MEX3A-KLF4 signaling axis that sustains cancer cells in undifferentiated and proliferative state."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Theranostics (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/thno.76619"}], "href": "https://doi.org/10.7150/thno.76619"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36276637"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36276637"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ana Domingo-Muelas, Pere Duart-Abadia, Jose Manuel Morante-Redolat, et al. 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