{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR-3151 is emerging as an important prognostic and functional player in acute myeloid leukemia (AML). Embedded within intron 1 of its host gene BAALC, elevated miR-3151 expression is associated with shorter disease‐free and overall survival in both cytogenetically normal and intermediate‐risk AML patients. Mechanistically, high levels of miR-3151 promote leukemogenesis by reducing apoptosis, in part through direct targeting of the 3′ untranslated region of TP53 and other proapoptotic regulators. In addition, miR-3151’s expression is partly uncoupled from BAALC and is coactivated by transcription factors such as the SP1/NF‑κB complex—with BAALC itself being further modulated by RUNX1—thus contributing to a combinatorial prognostic impact when both markers are assessed."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast, in chronic lymphocytic leukemia (CLL), miR-3151 appears to function as a tumor suppressor. Here, its promoter is frequently hypermethylated, leading to reduced miR-3151 expression and the consequent derepression of direct targets such as MAP-kinase activating death domain (MADD) and phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2). This loss of miR-3151 enables enhanced MEK/ERK and PI3K/AKT signaling, which protects CLL cells from apoptosis. Restoration of miR-3151 via demethylating treatment reactivates its tumor-suppressive functions by inhibiting proliferation and enhancing apoptotic pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, in solid tumors such as malignant melanoma and papillary thyroid cancer, where activating BRAF mutations are prevalent, miR-3151 expression is upregulated by the SP1/NF‑κB complex. In these contexts, miR-3151 acts as an oncomiR by directly targeting TP53, thereby diminishing its tumor suppressor activity and promoting cell survival. Importantly, knockdown of miR-3151 in these BRAF-mutated cancers leads to increased TP53 expression, enhanced nuclear localization, and caspase-3–dependent apoptosis, suggesting that combined inhibition of miR-3151 and mutant BRAF can synergize to improve therapeutic outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ann-Kathrin Eisfeld, Guido Marcucci, Kati Maharry, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-3151 interplays with its host gene BAALC and independently affects outcome of patients with cytogenetically normal acute myeloid leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2012-02-408492"}], "href": "https://doi.org/10.1182/blood-2012-02-408492"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22529287"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22529287"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ann-Kathrin Eisfeld, Sebastian Schwind, Ravi Patel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Intronic miR-3151 within BAALC drives leukemogenesis by deregulating the TP53 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.2004762"}], "href": "https://doi.org/10.1126/scisignal.2004762"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24736457"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24736457"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "M Díaz-Beyá, S Brunet, J Nomdedéu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood Cancer J (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/bcj.2015.76"}], "href": "https://doi.org/10.1038/bcj.2015.76"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26430723"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26430723"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Lu Qian Wang, Kwan Yeung Wong, Anders Rosèn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epigenetic silencing of tumor suppressor miR-3151 contributes to Chinese chronic lymphocytic leukemia by constitutive activation of MADD/ERK and PIK3R2/AKT signaling pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.6251"}], "href": "https://doi.org/10.18632/oncotarget.6251"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26517243"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26517243"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Malori A Lankenau, Ravi Patel, Sandya Liyanarachchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-3151 inactivates TP53 in BRAF-mutated human malignancies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1520390112"}], "href": "https://doi.org/10.1073/pnas.1520390112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26582795"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26582795"}]}]}]}