{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMicroRNA‐222, often coordinately expressed with miR‐221, has emerged as a potent oncogenic regulator in a broad spectrum of human malignancies. In endocrine‐responsive tumors such as breast, prostate, and thyroid cancers, elevated miR‐222 levels contribute to therapy resistance by directly targeting key cell cycle inhibitors (for example, p27Kip1), thereby facilitating unchecked cellular proliferation and diminished apoptotic responses. These effects underlie tamoxifen and fulvestrant resistance in breast cancer and promote androgen‐independent growth in prostate cancer, positioning miR‐222 as a promising predictive and therapeutic marker for aggressive disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in cell cycle deregulation, miR‐222 actively promotes tumor progression by inducing epithelial‐to‐mesenchymal transition (EMT), enhancing cell migration and invasion, and facilitating chemoresistance. It achieves this through the modulation of multiple signaling pathways—including NF‐κB, STAT3, and TGF‐β—and by downregulating transcriptional repressors that normally restrain the EMT. Moreover, miR‐222 is selectively loaded into exosomes that mediate intercellular communication; these extracellular vesicles transfer miR‐222 to surrounding cells, thereby disseminating oncogenic signals, promoting drug resistance, and even influencing the tumor microenvironment via macrophage polarization."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its well‐characterized roles in tumor cell proliferation and invasiveness, miR‐222 has been implicated in modulating immune responses, inflammation, and metabolic regulation. It influences the expression of adhesion molecules and immune checkpoints—thereby modulating interactions with cytotoxic lymphocytes—and has been associated with immune evasion in hematological malignancies such as chronic lymphocytic leukemia and myelodysplastic syndromes. Furthermore, deregulated miR‐222 impacts metabolic pathways in adipocytes and is linked to conditions such as gestational diabetes, underscoring its multifaceted role in both cancer pathogenesis and systemic metabolic control."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "43"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Silvia Galardi, Neri Mercatelli, Ezio Giorda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-221 and miR-222 expression affects the proliferation potential of human prostate carcinoma cell lines by targeting p27Kip1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M701805200"}], "href": "https://doi.org/10.1074/jbc.M701805200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17569667"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17569667"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jana K Gillies, Ian A J Lorimer "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of p27Kip1 by miRNA 221/222 in glioblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cc.6.16.4526"}], "href": "https://doi.org/10.4161/cc.6.16.4526"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17721077"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17721077"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Rosa Visone, Lucia Russo, Pierlorenzo Pallante, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNAs (miR)-221 and miR-222, both overexpressed in human thyroid papillary carcinomas, regulate p27Kip1 protein levels and cell cycle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocr Relat Cancer (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1677/ERC-07-0129"}], "href": "https://doi.org/10.1677/ERC-07-0129"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17914108"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17914108"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Tyler E Miller, Kalpana Ghoshal, Bhuvaneswari Ramaswamy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M804612200"}], "href": "https://doi.org/10.1074/jbc.M804612200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18708351"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18708351"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Neri Mercatelli, Valeria Coppola, Desirée Bonci, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The inhibition of the highly expressed miR-221 and miR-222 impairs the growth of prostate carcinoma xenografts in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0004029"}], "href": "https://doi.org/10.1371/journal.pone.0004029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19107213"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19107213"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Tong Sun, Qianben Wang, Steven Balk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of microRNA-221 and microRNA-222 in androgen-independent prostate cancer cell lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-08-4112"}], "href": "https://doi.org/10.1158/0008-5472.CAN-08-4112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19351832"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19351832"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Martijn Kedde, Marieke van Kouwenhove, Wilbert Zwart, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Pumilio-induced RNA structure switch in p27-3' UTR controls miR-221 and miR-222 accessibility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb2105"}], "href": "https://doi.org/10.1038/ncb2105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20818387"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20818387"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "X Rao, G Di Leva, M Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-221/222 confers breast cancer fulvestrant resistance by regulating multiple signaling pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2010.487"}], "href": "https://doi.org/10.1038/onc.2010.487"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21057537"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21057537"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yifang Wei, Xiaofeng Lai, Shentong Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosomal miR-221/222 enhances tamoxifen resistance in recipient ER-positive breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast Cancer Res Treat (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10549-014-3037-0"}], "href": "https://doi.org/10.1007/s10549-014-3037-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25007959"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25007959"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Susanna Stinson, Mark R Lackner, Alex T Adai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TRPS1 targeting by miR-221/222 promotes the epithelial-to-mesenchymal transition in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.2001538"}], "href": "https://doi.org/10.1126/scisignal.2001538"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21673316"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21673316"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "C Quintavalle, M Garofalo, C Zanca, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-221/222 overexpession in human glioblastoma increases invasiveness by targeting the protein phosphate PTPμ."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2011.280"}], "href": "https://doi.org/10.1038/onc.2011.280"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21743492"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21743492"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Magne Skårn, Heidi M Namløs, Paul Noordhuis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adipocyte differentiation of human bone marrow-derived stromal cells is modulated by microRNA-155, microRNA-221, and microRNA-222."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cells Dev (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/scd.2010.0503"}], "href": "https://doi.org/10.1089/scd.2010.0503"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21756067"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21756067"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Shanliang Zhong, Wenjing Li, Zhiyuan Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-222 and miR-29a contribute to the drug-resistance of breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2013.08.062"}], "href": "https://doi.org/10.1016/j.gene.2013.08.062"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23994196"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23994196"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Wei-xian Chen, Xue-min Liu, Meng-meng Lv, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosomes from drug-resistant breast cancer cells transmit chemoresistance by a horizontal transfer of microRNAs."}]}, {"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.0095240"}], "href": "https://doi.org/10.1371/journal.pone.0095240"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24740415"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24740415"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Sanhong Liu, Xiaohua Sun, Mingliang Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A microRNA 221- and 222-mediated feedback loop maintains constitutive activation of NFκB and STAT3 in colorectal cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastroenterology (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.gastro.2014.06.006"}], "href": "https://doi.org/10.1053/j.gastro.2014.06.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24931456"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24931456"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Felix Jansen, Xiaoyan Yang, Katharina Baumann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endothelial microparticles reduce ICAM-1 expression in a microRNA-222-dependent mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.12607"}], "href": "https://doi.org/10.1111/jcmm.12607"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26081516"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26081516"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Yunxing Xue, Zhe Wei, Hanying Ding, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-19b/221/222 induces endothelial cell dysfunction via suppression of PGC-1α in the progression of atherosclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Atherosclerosis (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.atherosclerosis.2015.06.031"}], "href": "https://doi.org/10.1016/j.atherosclerosis.2015.06.031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26117405"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26117405"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Annamaria Gullà, Maria Teresa Di Martino, Maria Eugenia Gallo Cantafio, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A 13 mer LNA-i-miR-221 Inhibitor Restores Drug Sensitivity in Melphalan-Refractory Multiple Myeloma Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-15-0489"}], "href": "https://doi.org/10.1158/1078-0432.CCR-15-0489"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26527748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26527748"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Federica Felicetti, Alessandra De Feo, Carolina Coscia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosome-mediated transfer of miR-222 is sufficient to increase tumor malignancy in melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Transl Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12967-016-0811-2"}], "href": "https://doi.org/10.1186/s12967-016-0811-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26912358"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26912358"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Xiang Ying, Quanfeng Wu, Xiaoli Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epithelial ovarian cancer-secreted exosomal miR-222-3p induces polarization of tumor-associated macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.9246"}], "href": "https://doi.org/10.18632/oncotarget.9246"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27172798"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27172798"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Feng Wei, Chengyuan Ma, Tong Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosomes derived from gemcitabine-resistant cells transfer malignant phenotypic traits via delivery of miRNA-222-3p."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12943-017-0694-8"}], "href": "https://doi.org/10.1186/s12943-017-0694-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28743280"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28743280"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Robin Verjans, Tim Peters, Francisco Javier Beaumont, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-221/222 Family Counteracts Myocardial Fibrosis in Pressure Overload-Induced Heart Failure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hypertension (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/HYPERTENSIONAHA.117.10094"}], "href": "https://doi.org/10.1161/HYPERTENSIONAHA.117.10094"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29255073"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29255073"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Ramon J Mayoral, Matthew E Pipkin, Mikhail Pachkov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-221-222 regulate the cell cycle in mast cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.182.1.433"}], "href": "https://doi.org/10.4049/jimmunol.182.1.433"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19109175"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19109175"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Ryo Ueda, Gary Kohanbash, Kotaro Sasaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dicer-regulated microRNAs 222 and 339 promote resistance of cancer cells to cytotoxic T-lymphocytes by down-regulation of ICAM-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0811817106"}], "href": "https://doi.org/10.1073/pnas.0811817106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19520829"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19520829"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Thomas Greither, Lukasz F Grochola, Andrej Udelnow, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.24687"}], "href": "https://doi.org/10.1002/ijc.24687"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19551852"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19551852"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Aina Pons, Benet Nomdedeu, Alfons Navarro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hematopoiesis-related microRNA expression in myelodysplastic syndromes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leuk Lymphoma (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3109/10428190903147645"}], "href": "https://doi.org/10.3109/10428190903147645"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19883312"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19883312"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Queenie W-L Wong, Arthur K-K Ching, Anthony W-H Chan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-222 overexpression confers cell migratory advantages in hepatocellular carcinoma through enhancing AKT signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-09-1840"}], "href": "https://doi.org/10.1158/1078-0432.CCR-09-1840"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20103675"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20103675"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Junxia Zhang, Lei Han, Youlin Ge, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-221/222 promote malignant progression of glioma through activation of the Akt pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo_00000570"}], "href": "https://doi.org/10.3892/ijo_00000570"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20198336"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20198336"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "John R Zibert, Marianne B Løvendorf, Thomas Litman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNAs and potential target interactions in psoriasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Dermatol Sci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jdermsci.2010.03.004"}], "href": "https://doi.org/10.1016/j.jdermsci.2010.03.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20417062"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20417062"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Patrizia Dentelli, Arturo Rosso, Francesca Orso, et al. "}, {"type": "b", "children": [{"type": "t", "text": "microRNA-222 controls neovascularization by regulating signal transducer and activator of transcription 5A expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/ATVBAHA.110.206201"}], "href": "https://doi.org/10.1161/ATVBAHA.110.206201"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20489169"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20489169"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Manuela Ferracin, Barbara Zagatti, Lara Rizzotto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNAs involvement in fludarabine refractory chronic lymphocytic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1476-4598-9-123"}], "href": "https://doi.org/10.1186/1476-4598-9-123"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20504344"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20504344"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Chun-Zhi Zhang, Jun-Xia Zhang, An-Ling Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1476-4598-9-229"}], "href": "https://doi.org/10.1186/1476-4598-9-229"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20813046"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20813046"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Chunzhi Zhang, Junxia Zhang, Anlin Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PUMA is a novel target of miR-221/222 in human epithelial cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo_00000816"}], "href": "https://doi.org/10.3892/ijo_00000816"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21042732"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21042732"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Linwah Yip, Lindsey Kelly, Yongli Shuai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA signature distinguishes the degree of aggressiveness of papillary thyroid carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Surg Oncol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1245/s10434-011-1733-0"}], "href": "https://doi.org/10.1245/s10434-011-1733-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21537871"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21537871"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "M Acunzo, R Visone, G Romano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-130a targets MET and induces TRAIL-sensitivity in NSCLC by downregulating miR-221 and 222."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2011.260"}], "href": "https://doi.org/10.1038/onc.2011.260"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21706050"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21706050"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Tomohiro Ogawa, Masaru Enomoto, Hideki Fujii, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-221/222 upregulation indicates the activation of stellate cells and the progression of liver fibrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gut (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/gutjnl-2011-300717"}], "href": "https://doi.org/10.1136/gutjnl-2011-300717"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22267590"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22267590"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Ioannis Pandis, Caroline Ospelt, Niki Karagianni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of microRNA-221/222 and microRNA-323-3p association with rheumatoid arthritis via predictions using the human tumour necrosis factor transgenic mouse model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Rheum Dis (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/annrheumdis-2011-200803"}], "href": "https://doi.org/10.1136/annrheumdis-2011-200803"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22562984"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22562984"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Miki Fuse, Satoko Kojima, Hideki Enokida, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumor suppressive microRNAs (miR-222 and miR-31) regulate molecular pathways based on microRNA expression signature in prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jhg.2012.95"}], "href": "https://doi.org/10.1038/jhg.2012.95"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22854542"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22854542"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "James C Lee, Jing Ting Zhao, Roderick J Clifton-Bligh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-222 and microRNA-146b are tissue and circulating biomarkers of recurrent papillary thyroid cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cncr.28254"}], "href": "https://doi.org/10.1002/cncr.28254"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24301304"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24301304"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Zhonghua Shi, Chun Zhao, Xirong Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential expression of microRNAs in omental adipose tissue from gestational diabetes mellitus subjects reveals miR-222 as a regulator of ERα expression in estrogen-induced insulin resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2013-2046"}], "href": "https://doi.org/10.1210/en.2013-2046"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24601884"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24601884"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Wei Long, Chun Zhao, Chenbo Ji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of serum microRNAs profile of PCOS and identification of novel non-invasive biomarkers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Physiol Biochem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000358698"}], "href": "https://doi.org/10.1159/000358698"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24802714"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24802714"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Xihe Zhao, Ping Wang, Jing Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gas5 Exerts Tumor-suppressive Functions in Human Glioma Cells by Targeting miR-222."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Ther (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/mt.2015.170"}], "href": "https://doi.org/10.1038/mt.2015.170"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26370254"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26370254"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Zhonghu Li, Yang Tao, Xiaoya Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumor-Secreted Exosomal miR-222 Promotes Tumor Progression via Regulating P27 Expression and Re-Localization in Pancreatic Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Physiol Biochem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000495281"}], "href": "https://doi.org/10.1159/000495281"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30458449"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30458449"}]}]}]}