{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMIR4673 is a microRNA transcribed from the Notch‐1 locus that functions as a key regulator of cell cycle progression by targeting cyclin‐dependent kinase 18 (cdk‐18). In mammary carcinoma cells (SKBR3), MIR4673 downregulates cdk‐18 triggering mitophagy and autophagy. This cascade results in the proteasomal degradation of p53, a reprogramming of estrogen receptor and progesterone receptor status, and a transient arrest of cycling cells in the G0 phase. These changes effectively enhance the resistance of neoplastic cells to radiation and contribute to their improved fitness during therapeutic challenges."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn parallel, MIR4673 plays a pivotal role in human neurogenesis by modulating the proliferative capacity of neural progenitor cells. Here, the microRNA exerts a bimodal reprogramming effect on the cell cycle: it transiently inhibits cdk‐18 to synchronize neural precursors at the G0 phase, and it accelerates progression through interphase. This coordinated reprogramming is accompanied by autophagic degradation of critical regulators (such as p53/p21) and silencing of checkpoint proteins (e.g., XRCC3/BRCA2), which together amplify cell proliferation while delaying differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kağan Dökümcü, Mary Simonian, Ramin M Farahani "}, {"type": "b", "children": [{"type": "t", "text": "miR4673 improves fitness profile of neoplastic cells by induction of autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-018-1088-6"}], "href": "https://doi.org/10.1038/s41419-018-1088-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30341280"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30341280"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ramin Farahani, Saba Rezaei-Lotfi, Mary Simonian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bi-modal reprogramming of cell cycle by MiRNA-4673 amplifies human neurogenic capacity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15384101.2019.1595873"}], "href": "https://doi.org/10.1080/15384101.2019.1595873"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30907228"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30907228"}]}]}]}