{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMIR99AHG is a long noncoding RNA that serves as the host gene for a microRNA cluster, with its function initially remaining elusive in diseases such as acute megakaryoblastic leukemia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Recent evidence, however, implicates MIR99AHG in several key regulatory processes in both oncologic and infectious contexts.\n \nIn lung adenocarcinoma, MIR99AHG acts as a noncoding tumor suppressor. It is downregulated in tumor tissues partly due to copy number deletions, and its reduced expression correlates with poor patient survival. Functionally, MIR99AHG suppresses cell proliferation and metastasis while promoting autophagy by interacting with ANXA2 to accelerate ATG16L+ vesicle biogenesis, and through the coordinated action of its co-expressed miR-99a, which targets mTOR."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n \nIn the context of tuberculosis infection, MIR99AHG—termed lincRNA-MIR99AHG in this setting—is upregulated upon IL-4/IL-13 stimulation in macrophages. However, its expression is downregulated upon Mycobacterium tuberculosis infection, and experimental knockdown leads to reduced intracellular mycobacterial growth and diminished pro-inflammatory cytokine production. These findings suggest that MIR99AHG acts as a positive regulator of inflammation and macrophage polarization that ultimately promotes bacterial survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n \nBy contrast, in colorectal cancer, MIR99AHG seems to play a pro-metastatic role. It is highly expressed in invasive cancer cells and metastatic tumors, where it binds to and stabilizes the splicing factor PTBP1. This interaction alters the alternative splicing of SMARCA1 pre-mRNA, favoring the production of the SMARCA1-L isoform that lacks the suppressive effects on cell migration, invadopodia formation, and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n \nWhile its molecular functions have been more clearly defined in lung adenocarcinoma, tuberculosis, and colorectal cancer, investigations in breast"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "and endometrial cancers"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "indicate that additional studies are needed to fully elucidate the diverse roles of MIR99AHG in tumorigenesis and immune modulation.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stephan Emmrich, Alexandra Streltsov, Franziska Schmidt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LincRNAs MONC and MIR100HG act as oncogenes in acute megakaryoblastic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1476-4598-13-171"}], "href": "https://doi.org/10.1186/1476-4598-13-171"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25027842"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25027842"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Chencheng Han, Hong Li, Zhifei Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MIR99AHG is a noncoding tumor suppressor gene in lung adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-021-03715-7"}], "href": "https://doi.org/10.1038/s41419-021-03715-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33931593"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33931593"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lorna Gcanga, Ousman Tamgue, Mumin Ozturk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Host-Directed Targeting of LincRNA-MIR99AHG Suppresses Intracellular Growth of "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "Mycobacterium tuberculosis"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": "."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acid Ther (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/nat.2022.0009"}], "href": "https://doi.org/10.1089/nat.2022.0009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35895506"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35895506"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Danxiu Li, Xin Wang, Hui Miao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The lncRNA MIR99AHG directs alternative splicing of "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SMARCA1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " by PTBP1 to enable invadopodia formation in colorectal cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.adh4210"}], "href": "https://doi.org/10.1126/scisignal.adh4210"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37725664"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37725664"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Rong Guo, Yonghui Su, Qi Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LINC00478-derived novel cytoplasmic lncRNA LacRNA stabilizes PHB2 and suppresses breast cancer metastasis via repressing MYC targets."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Transl Med (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12967-023-03967-1"}], "href": "https://doi.org/10.1186/s12967-023-03967-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36782197"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36782197"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yingyi Feng, Yongshun Dong, Boqi Rao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel LINC00478 serves as a tumor suppressor in endometrial carcinoma progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cancer Res Clin Oncol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00432-023-05282-0"}], "href": "https://doi.org/10.1007/s00432-023-05282-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37603104"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37603104"}]}]}]}