{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMiR‐1246 has emerged as a multifunctional non‐coding RNA critically involved in cancer biology. In several tumor types—including colon, glioma, breast, prostate, lung, oral, colorectal, liver, cervical, and pancreatic cancers—it is frequently enriched in tumor‐derived exosomes and/or upregulated in cancer stem cells, thereby modulating the tumor microenvironment. For instance, mutant p53‐harboring colon cancer cells shed miR‐1246–laden exosomes that reprogram macrophages toward an anti‐inflammatory, tumor‐supportive phenotype, while in hypoxic gliomas miR‐1246–rich exosomes drive M2 polarization through suppression of TERF2IP. In prostate cancer, intracellular miR‐1246 acts as a tumor suppressor yet is selectively released in exosomes, and in lung cancer it functions as a driver of tumor initiation and metastasis through effects on cancer stem cells. Additional studies have demonstrated that miR‐1246 promotes motility in oral cancer via DENN/MADD Domain Containing 2D (DENND2D) inhibition, enhances liver cancer stemness by activating the Wnt/β‐catenin pathway via suppression of AXIN2 and GSK3β, and upregulates pro‐inflammatory mediators in breast mesenchymal stromal cells. Collectively, these findings underscore the critical role of miR‐1246 in promoting cancer progression, invasion, metastasis, and the establishment of a tumor‐promoting immunosuppressive microenvironment."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic studies have further revealed that miR‐1246 not only exerts its functions through a spectrum of direct targets but also exhibits non‐canonical biogenesis. It originates as a degradation product of RNU2-1 rather than from the classical Drosha/Dicer pathway, a finding that helps explain its remarkable enrichment in exosomes derived from malignant cells. Furthermore, miR‐1246 modulates key signaling axes such as DR5 in lung cancer to confer radioresistance and influences inflammatory as well as stemness pathways in various settings—it targets TERF2IP, regulates DYRK1A downstream of p53-family activation, and modulates the STAT3 pathway via LRIG1 in acute myeloid leukemia. Its presence in circulating body fluids (serum, urine, saliva, cerebrospinal fluid) has rendered it a promising non‐invasive biomarker for early diagnosis and prognostication across multiple cancers, including cervical, bladder, pancreatic, and esophageal malignancies. These diverse mechanistic insights, obtained from studies addressing hepatic ischemia/reperfusion injury, inflammatory bowel disease, and therapeutic response prediction, underscore the multifaceted roles of miR-1246 as both a functional mediator and a robust biomarker."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "38"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond oncological settings, miR‐1246 plays significant roles in diverse non‐cancerous physiological and pathological processes. In cardiovascular and musculoskeletal systems, exosomal miR‐1246 from mesenchymal stem cells has been shown to alleviate hepatic ischemia/reperfusion injury and improve cardiac function via modulation of the IL‑6/gp130‑STAT3 and PRSS23/Snail signaling pathways. It also participates in osteoarthritis pathogenesis by regulating inflammatory mediators, influences corneal neovascularization through a MIAT/ACE axis, and is implicated in hemophilia A by modulating factor VIII expression. Moreover, its protective functions have been documented in skin photoaging, where miR‐1246–enriched adipose‑derived stem cell exosomes attenuate UVB‑induced damage, and in thyroid cancer where it suppresses tumor growth by targeting the PI3K adapter PIK3AP1. These studies highlight miR‑1246 as a pleiotropic regulator whose dysregulation contributes not only to cancer but also to diverse systemic pathologies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "39", "end_ref": "49"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tomer Cooks, Ioannis S Pateras, Lisa M Jenkins, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-03224-w"}], "href": "https://doi.org/10.1038/s41467-018-03224-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29472616"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29472616"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Mingyu Qian, Shaobo Wang, Xiaofan Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypoxic glioma-derived exosomes deliver microRNA-1246 to induce M2 macrophage polarization by targeting TERF2IP via the STAT3 and NF-κB pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-019-0996-y"}], "href": "https://doi.org/10.1038/s41388-019-0996-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31485019"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31485019"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xiu Juan Li, Zhao Jun Ren, Jin Hai Tang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosomal MicroRNA MiR-1246 Promotes Cell Proliferation, Invasion and Drug Resistance by Targeting CCNG2 in Breast Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Physiol Biochem (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000485780"}], "href": "https://doi.org/10.1159/000485780"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29216623"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29216623"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Divya Bhagirath, Thao Ly Yang, Nathan Bucay, et al. "}, {"type": "b", "children": [{"type": "t", "text": "microRNA-1246 Is an Exosomal Biomarker for Aggressive Prostate Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-17-2069"}], "href": "https://doi.org/10.1158/0008-5472.CAN-17-2069"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29437039"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29437039"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Wen Cai Zhang, Tan Min Chin, Henry Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumour-initiating cell-specific miR-1246 and miR-1290 expression converge to promote non-small cell lung cancer progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms11702"}], "href": "https://doi.org/10.1038/ncomms11702"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27325363"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27325363"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sujata Sakha, Tomoki Muramatsu, Koji Ueda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosomal microRNA miR-1246 induces cell motility and invasion through the regulation of DENND2D in oral squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep38750"}], "href": "https://doi.org/10.1038/srep38750"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27929118"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27929118"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Stella Chai, Kai-Yu Ng, Man Tong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Octamer 4/microRNA-1246 signaling axis drives Wnt/β-catenin activation in liver cancer stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.28821"}], "href": "https://doi.org/10.1002/hep.28821"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27639189"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27639189"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Nami Yamada, Nonoka Tsujimura, Minami Kumazaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Colorectal cancer cell-derived microvesicles containing microRNA-1246 promote angiogenesis by activating Smad 1/5/8 signaling elicited by PML down-regulation in endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbagrm.2014.09.002"}], "href": "https://doi.org/10.1016/j.bbagrm.2014.09.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25218966"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25218966"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "S Hasegawa, H Eguchi, H Nagano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Cancer (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/bjc.2014.454"}], "href": "https://doi.org/10.1038/bjc.2014.454"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25117811"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25117811"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Ling-Yan Zhai, Min-Xiang Li, Wei-Lun Pan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In Situ Detection of Plasma Exosomal MicroRNA-1246 for Breast Cancer Diagnostics by a Au Nanoflare Probe."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "ACS Appl Mater Interfaces (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/acsami.8b12725"}], "href": "https://doi.org/10.1021/acsami.8b12725"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30350935"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30350935"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Gwangil Kim, Hee-Jung An, Mi-Jung Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hsa-miR-1246 and hsa-miR-1290 are associated with stemness and invasiveness of non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lung Cancer (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.lungcan.2015.11.013"}], "href": "https://doi.org/10.1016/j.lungcan.2015.11.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26711929"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26711929"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Zhao Sun, Changting Meng, Shihua Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-1246 enhances migration and invasion through CADM1 in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2407-14-616"}], "href": "https://doi.org/10.1186/1471-2407-14-616"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25159494"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25159494"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Dexiao Yuan, Jinping Xu, Juan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Extracellular miR-1246 promotes lung cancer cell proliferation and enhances radioresistance by directly targeting DR5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.9017"}], "href": "https://doi.org/10.18632/oncotarget.9017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27129166"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27129166"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Li-Jun Mo, Man Song, Qiao-Hua Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosome-packaged miR-1246 contributes to bystander DNA damage by targeting LIG4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Cancer (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41416-018-0192-9"}], "href": "https://doi.org/10.1038/s41416-018-0192-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30038324"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30038324"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Fan Yang, Hairong Xiong, Li Duan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-1246 Promotes Metastasis and Invasion of A549 cells by Targeting GSK-3β‒Mediated Wnt/β-Catenin Pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res Treat (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4143/crt.2018.638"}], "href": "https://doi.org/10.4143/crt.2018.638"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30913872"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30913872"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Wei Qiu, Xiaofan Guo, Boyan Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosomal miR-1246 from glioma patient body fluids drives the differentiation and activation of myeloid-derived suppressor cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Ther (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymthe.2021.06.023"}], "href": "https://doi.org/10.1016/j.ymthe.2021.06.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34217892"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34217892"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Alexander Bott, Nese Erdem, Shalom Lerrer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miRNA-1246 induces pro-inflammatory responses in mesenchymal stem/stromal cells by regulating PKA and PP2A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.14915"}], "href": "https://doi.org/10.18632/oncotarget.14915"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28159925"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28159925"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Sai Wang, Ya Zeng, Ju-Mei Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-1246 promotes growth and metastasis of colorectal cancer cells involving CCNG2 reduction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2015.4557"}], "href": "https://doi.org/10.3892/mmr.2015.4557"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26573378"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26573378"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Jun-Ming Liao, Xiang Zhou, Yu Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-1246: a new link of the p53 family with cancer and Down syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cc.20809"}], "href": "https://doi.org/10.4161/cc.20809"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22751441"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22751441"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Junying Chen, Desheng Yao, Shan Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-1246 promotes SiHa cervical cancer cell proliferation, invasion, and migration through suppression of its target gene thrombospondin 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Gynecol Obstet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00404-014-3260-2"}], "href": "https://doi.org/10.1007/s00404-014-3260-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24806621"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24806621"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Yi-Fan Xu, Bethany N Hannafon, Ujjwol Khatri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The origin of exosomal miR-1246 in human cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15476286.2019.1585738"}], "href": "https://doi.org/10.1080/15476286.2019.1585738"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30806147"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30806147"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Kun Xie, Lei Liu, Jiangming Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosomal miR-1246 derived from human umbilical cord blood mesenchymal stem cells attenuates hepatic ischemia reperfusion injury by modulating T helper 17/regulatory T balance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "IUBMB Life (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/iub.2147"}], "href": "https://doi.org/10.1002/iub.2147"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31433911"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31433911"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Jae-Hyeon Kim, Jun-Ho Ahn, Michael Lee "}, {"type": "b", "children": [{"type": "t", "text": "Upregulation of MicroRNA-1246 Is Associated with BRAF Inhibitor Resistance in Melanoma Cells with Mutant BRAF."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res Treat (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4143/crt.2016.280"}], "href": "https://doi.org/10.4143/crt.2016.280"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28052651"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28052651"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Jin-Long Huang, Yi-Peng Fu, Wei Gan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepatic stellate cells promote the progression of hepatocellular carcinoma through microRNA-1246-RORα-Wnt/β-Catenin axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2020.02.012"}], "href": "https://doi.org/10.1016/j.canlet.2020.02.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32061951"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32061951"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Kun Xie, Lei Liu, Jiangming Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosomes derived from human umbilical cord blood mesenchymal stem cells improve hepatic ischemia reperfusion injury via delivering miR-1246."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15384101.2019.1689480"}], "href": "https://doi.org/10.1080/15384101.2019.1689480"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31709894"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31709894"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Geoffrey W Krissansen, Yi Yang, Fiona M McQueen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of miR-595 and miR-1246 in the sera of patients with active forms of inflammatory bowel disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Inflamm Bowel Dis (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MIB.0000000000000285"}], "href": "https://doi.org/10.1097/MIB.0000000000000285"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25628040"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25628040"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Zhen Zhang, Luoyan Zhang, Guoxiang Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosomal miR-1246 and miR-155 as predictive and prognostic biomarkers for trastuzumab-based therapy resistance in HER2-positive breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Chemother Pharmacol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00280-020-04168-z"}], "href": "https://doi.org/10.1007/s00280-020-04168-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33068176"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33068176"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Y Yang, Y J Xie, Q Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Down-regulation of miR-1246 in cervical cancer tissues and its clinical significance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gynecol Oncol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ygyno.2015.06.015"}], "href": "https://doi.org/10.1016/j.ygyno.2015.06.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26074491"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26074491"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Ran Xu, Huabing Li, Shuiqing Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-1246 regulates the radio-sensitizing effect of curcumin in bladder cancer cells via activating P53."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int Urol Nephrol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11255-019-02210-5"}], "href": "https://doi.org/10.1007/s11255-019-02210-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31236854"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31236854"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Li-Juan Xu, Tao Jiang, Wei Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Parallel mRNA and microRNA profiling of HEV71-infected human neuroblastoma cells reveal the up-regulation of miR-1246 in association with DLG3 repression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0095272"}], "href": "https://doi.org/10.1371/journal.pone.0095272"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24739954"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24739954"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Panpan Liu, Qun Zhang, Jun Mi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosomes derived from stem cells of human deciduous exfoliated teeth inhibit angiogenesis in vivo and in vitro via the transfer of miR-100-5p and miR-1246."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cell Res Ther (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13287-022-02764-9"}], "href": "https://doi.org/10.1186/s13287-022-02764-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35241153"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35241153"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Mingyu Qian, Zihang Chen, Xiaofan Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosomes derived from hypoxic glioma deliver miR-1246 and miR-10b-5p to normoxic glioma cells to promote migration and invasion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lab Invest (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41374-020-00522-0"}], "href": "https://doi.org/10.1038/s41374-020-00522-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33446893"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33446893"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Kevin Tak-Pan Ng, Chung Mau Lo, Nathalie Wong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Early-phase circulating miRNAs predict tumor recurrence and survival of hepatocellular carcinoma patients after liver transplantation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.7627"}], "href": "https://doi.org/10.18632/oncotarget.7627"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26918346"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26918346"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Sribalasubashini Muralimanoharan, Youn-Tae Kwak, Carole R Mendelson "}, {"type": "b", "children": [{"type": "t", "text": "Redox-Sensitive Transcription Factor NRF2 Enhances Trophoblast Differentiation via Induction of miR-1246 and Aromatase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2017-03024"}], "href": "https://doi.org/10.1210/en.2017-03024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29546425"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29546425"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "MiaoMiao Sheng, Ying Zhong, Yang Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p inhibitors can reduce the cytotoxicity of Ebola virus glycoprotein in vitro."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci China Life Sci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11427-014-4742-y"}], "href": "https://doi.org/10.1007/s11427-014-4742-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25218824"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25218824"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Wei Li, Ya-Fen Wu, Rong-Hua Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-1246 releases RTKN2-dependent resistance to UVB-induced apoptosis in HaCaT cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-014-2108-1"}], "href": "https://doi.org/10.1007/s11010-014-2108-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24880483"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24880483"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Lan Liao, Jun Wang, Shaobo Ouyang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and clinical significance of microRNA-1246 in human oral squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Med Sci Monit (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.12659/MSM.892508"}], "href": "https://doi.org/10.12659/MSM.892508"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25791131"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25791131"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Fumitaka Ishige, Isamu Hoshino, Yosuke Iwatate, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MIR1246 in body fluids as a biomarker for pancreatic cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-020-65695-6"}], "href": "https://doi.org/10.1038/s41598-020-65695-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32457495"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32457495"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Zicheng Wang, Da Gao, Shengjie Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosomal microRNA-1246 from human umbilical cord mesenchymal stem cells potentiates myocardial angiogenesis in chronic heart failure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biol Int (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cbin.11664"}], "href": "https://doi.org/10.1002/cbin.11664"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34270841"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34270841"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Ke Qi, Rongqiang Lin, Chenchen Xue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long Non-Coding RNA (LncRNA) CAIF is Downregulated in Osteoarthritis and Inhibits LPS-Induced Interleukin 6 (IL-6) Upregulation by Downregulation of MiR-1246."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Med Sci Monit (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.12659/MSM.917135"}], "href": "https://doi.org/10.12659/MSM.917135"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31653823"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31653823"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Chisaho Torii, Nako Maishi, Taisuke Kawamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miRNA-1246 in extracellular vesicles secreted from metastatic tumor induces drug resistance in tumor endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-021-92879-5"}], "href": "https://doi.org/10.1038/s41598-021-92879-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34226586"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34226586"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Chia-Ming Liu, Yi-Wen Liao, Pei-Ling Hsieh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-1246 as a therapeutic target in oral submucosa fibrosis pathogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Formos Med Assoc (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jfma.2019.02.014"}], "href": "https://doi.org/10.1016/j.jfma.2019.02.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30928188"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30928188"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Tewarit Sarachana, Neetu Dahiya, Vijaya L Simhadri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Small ncRNA Expression-Profiling of Blood from Hemophilia A Patients Identifies miR-1246 as a Potential Regulator of Factor 8 Gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0132433"}], "href": "https://doi.org/10.1371/journal.pone.0132433"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26176629"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26176629"}]}, {"type": "r", "ref": 44, "children": [{"type": "t", "text": "Qiang Huang, Chi-Yao Hsueh, Yang Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lack of miR-1246 in small extracellular vesicle blunts tumorigenesis of laryngeal carcinoma cells by regulating Cyclin G2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "IUBMB Life (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/iub.2274"}], "href": "https://doi.org/10.1002/iub.2274"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32196930"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32196930"}]}, {"type": "r", "ref": 45, "children": [{"type": "t", "text": "Wei Gao, Li-Min Yuan, Yue Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-1246-overexpressing exosomes suppress UVB-induced photoaging via regulation of TGF-β/Smad and attenuation of MAPK/AP-1 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Photochem Photobiol Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s43630-022-00304-1"}], "href": "https://doi.org/10.1007/s43630-022-00304-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36114328"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36114328"}]}, {"type": "r", "ref": 46, "children": [{"type": "t", "text": "Lijuan Chen, Zhi Guo, Yongming Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "microRNA-1246-containing extracellular vesicles from acute myeloid leukemia cells promote the survival of leukemia stem cells via the LRIG1-meditated STAT3 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.202893"}], "href": "https://doi.org/10.18632/aging.202893"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33893245"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33893245"}]}, {"type": "r", "ref": 47, "children": [{"type": "t", "text": "Isamu Hoshino, Hajime Yokota, Fumitaka Ishige, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Radiogenomics predicts the expression of microRNA-1246 in the serum of esophageal cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-020-59500-7"}], "href": "https://doi.org/10.1038/s41598-020-59500-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32054931"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32054931"}]}, {"type": "r", "ref": 48, "children": [{"type": "t", "text": "Yanhui Bai, Weiqun Wang, Youmei Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "lncRNA MIAT suppression alleviates corneal angiogenesis through regulating miR-1246/ACE."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15384101.2019.1578143"}], "href": "https://doi.org/10.1080/15384101.2019.1578143"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30782069"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30782069"}]}, {"type": "r", "ref": 49, "children": [{"type": "t", "text": "Jingyan Li, Zhanlei Zhang, Jieting Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-1246 regulates the PI3K/AKT signaling pathway by targeting PIK3AP1 and inhibits thyroid cancer cell proliferation and tumor growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-021-04290-3"}], "href": "https://doi.org/10.1007/s11010-021-04290-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34870753"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34870753"}]}]}]}