{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nA growing body of evidence indicates that miR-612 functions predominantly as a tumor‐suppressive microRNA in several solid tumors. In hepatocellular carcinoma, colorectal cancer, bladder cancer, and melanoma, miR‑612 inhibits cell proliferation, migration, invasion, epithelial–mesenchymal transition, metastasis, cancer stemness, and chemoresistance by directly targeting oncogenic factors such as AKT2, Sp1, and other mediators of the Wnt/β‑catenin pathway. Its low expression correlates with increased tumor size, advanced stages, and poorer prognosis, while forced overexpression suppresses these aggressive behaviors in both in vitro and in vivo models."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional studies have revealed that miR‑612 expression and activity are tightly controlled by its genomic context and by interactions with other noncoding RNAs. Genetic variants within its precursor (for example, single nucleotide polymorphisms) can modulate its mature levels in a cell type–specific fashion, while long noncoding RNAs such as LINC01061 function as competing endogenous RNAs that bind miR‑612. In other settings, aberrant miR‑612 levels contribute to dysregulation of key targets such as TP53, FAIM2, and BRD4—thereby promoting oncogenic features in esophageal squamous cell carcinoma, neurofibromatosis‐associated tumors, and autoimmune thyroid disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, miR‑612 plays a notable role in the regulation of angiogenesis. In the context of hypoxic mesenchymal stem cell–derived extracellular vesicles, increased levels of miR‑612 promote angiogenic activities by repressing TP53, which in turn enhances paracrine HIF‑1α–VEGF signaling. This mechanistic insight points to the therapeutic potential of miR‑612 transfer in ischemic diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zhong-Hua Tao, Jin-Liang Wan, Ling-Yao Zeng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-612 suppresses the invasive-metastatic cascade in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20120153"}], "href": "https://doi.org/10.1084/jem.20120153"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23478189"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23478189"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jun Tang, Zhong-Hua Tao, Duo Wen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-612 suppresses the stemness of liver cancer via Wnt/β-catenin signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2014.03.135"}], "href": "https://doi.org/10.1016/j.bbrc.2014.03.135"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24704424"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24704424"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "L Sheng, P He, X Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-612 negatively regulates colorectal cancer growth and metastasis by targeting AKT2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2015.184"}], "href": "https://doi.org/10.1038/cddis.2015.184"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26158514"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26158514"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yang Liu, Dong-Li Liu, Li-Li Dong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-612 suppresses stem cell-like property of hepatocellular carcinoma cells by modulating Sp1/Nanog signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2016.282"}], "href": "https://doi.org/10.1038/cddis.2016.282"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27685621"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27685621"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ying Zhu, Hao-Liang Zhang, Qi-Ying Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of microRNA-612 Restrains the Growth, Invasion, and Tumorigenesis of Melanoma Cells by Targeting Espin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cells (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.14348/molcells.2018.2235"}], "href": "https://doi.org/10.14348/molcells.2018.2235"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29385671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29385671"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mengnan Liu, Yifan Chen, Bisheng Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumor-suppressing effects of microRNA-612 in bladder cancer cells by targeting malic enzyme 1 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2018.4342"}], "href": "https://doi.org/10.3892/ijo.2018.4342"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29620192"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29620192"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yang Liu, Li-Li Lu, Duo Wen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-612 regulates invadopodia of hepatocellular carcinoma by HADHA-mediated lipid reprogramming."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hematol Oncol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13045-019-0841-3"}], "href": "https://doi.org/10.1186/s13045-019-0841-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32033570"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32033570"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hye Kyung Kim, Ludmila Prokunina-Olsson, Stephen J Chanock "}, {"type": "b", "children": [{"type": "t", "text": "Common genetic variants in miR-1206 (8q24.2) and miR-612 (11q13.3) affect biogenesis of mature miRNA forms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0047454"}], "href": "https://doi.org/10.1371/journal.pone.0047454"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23077621"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23077621"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Ping Zhou, He Dong, Shuqian He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR612 is associated with esophageal squamous cell carcinoma development and metastasis, mediated through TP53."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2017.6808"}], "href": "https://doi.org/10.3892/mmr.2017.6808"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28656264"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28656264"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Aijun Yu, Luwen Zhao, Qingmin Kang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA LINC01061 sponges miR-612 to regulate the oncogenic role of SEMA4D in cholangiocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2019.03.125"}], "href": "https://doi.org/10.1016/j.bbrc.2019.03.125"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30967271"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30967271"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Meng Wang, Zengtao Wang, Xiaolei Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NFKB1-miR-612-FAIM2 pathway regulates tumorigenesis in neurofibromatosis type 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "In Vitro Cell Dev Biol Anim (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11626-019-00370-3"}], "href": "https://doi.org/10.1007/s11626-019-00370-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31197610"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31197610"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Yuhang Zhao, Lili Xu, Qing Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LINC01061 triggers inflammation and inflammasome activation in autoimmune thyroiditis via microRNA-612/BRD4 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int Immunopharmacol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.intimp.2022.109050"}], "href": "https://doi.org/10.1016/j.intimp.2022.109050"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35998503"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35998503"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Lite Ge, Chengfeng Xun, Wenshui Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Extracellular vesicles derived from hypoxia-preconditioned olfactory mucosa mesenchymal stem cells enhance angiogenesis via miR-612."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Nanobiotechnology (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12951-021-01126-6"}], "href": "https://doi.org/10.1186/s12951-021-01126-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34802444"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34802444"}]}]}]}