{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have demonstrated that MIRLET7E plays a critical role in fine‐tuning inflammatory and innate immune responses. In the intestinal mucosa, binding of MIRLET7E to the 3′‐UTR of IL‐23R normally results in repression of receptor over‐expression, and loss of this binding may sustain proinflammatory signaling in inflammatory bowel disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In peripheral immune cells, MIRLET7E is part of a microRNA cluster that is induced by Toll‐like receptor activation, thereby broadly regulating cytokine production and contributing to endotoxin tolerance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Its expression is modulated in neuropsychiatric and autoimmune conditions as well—levels in peripheral blood mononuclear cells inversely correlate with depression severity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", and increased MIRLET7E in autoimmune thyroid disorders is associated with altered intracellular IL-10 expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, in vascular endothelial cells MIRLET7E promotes NF-κB activation and modulates IL-6 signaling, while in cerebrospinal fluid extracellular members of the MIRLET7 family, including MIRLET7E, mediate neurotoxic effects."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMIRLET7E also exhibits potent regulatory functions in cancer, acting in context‐dependent tumor suppressive and oncogenic manners. In breast cancer cells, epigenetic repression of MIRLET7E by the histone demethylase JARID1B relieves its inhibition of cyclin D1, thereby promoting cell cycle progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In glioma stem cells, downregulation of MIRLET7E by the long non‐coding RNA NEAT1 results in elevated NRAS expression and enhanced oncogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In esophageal squamous cell carcinoma, overexpression of a miRNA cluster containing MIRLET7E augments metastatic potential."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " In non‐small cell lung cancer, upregulation of MIRLET7E via cofilin-1 overexpression suppresses tumor growth and invasion, and serum-derived exosomal MIRLET7E has been shown to inhibit oncogenic SUV39H2 signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " In colorectal cancer, diminished MIRLET7E contributes to enhanced IGF1R and ST8SIA1 expression, leading to increased proliferation and invasiveness."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " In ovarian cancer, deregulated MIRLET7E is associated with platinum resistance through alleviation of its inhibitory effects on DNA repair mediators, while a distinct study also linked reduced MIRLET7E to chemoresistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": " Finally, a single nucleotide polymorphism that disrupts the binding of MIRLET7E to IL-23R has been correlated with increased cancer risk, emphasizing its dual role at the interface of immune regulation and oncogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its mechanistic contributions to immune and tumor cell behavior, MIRLET7E holds promise as a diagnostic and prognostic biomarker in diverse clinical settings. Altered levels of MIRLET7E in serum have been associated with osteoarthritis progression"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": ", while variations in urinary concentrations of let-7 family miRNAs may aid in the early detection of renal cell carcinoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": " In endocrine disorders such as polycystic ovary syndrome, elevated expression of MIRLET7E in granulosa cells promotes aberrant proliferation and suppresses autophagy via the p21 pathway, implicating it in the pathogenesis of non-hyperandrogenic PCOS."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": " Moreover, comprehensive reviews have highlighted the versatile roles of MIRLET7E—not only as a regulator of inflammatory and oncogenic signaling but also as a potential therapeutic target—in precision medicine across cancer and degenerative diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Antonie Zwiers, Laurens Kraal, Tineke C T M van de Pouw Kraan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cutting edge: a variant of the IL-23R gene associated with inflammatory bowel disease induces loss of microRNA regulation and enhanced protein production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1101494"}], "href": "https://doi.org/10.4049/jimmunol.1101494"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22262659"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22262659"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tomoya Kagawa, Mikio Watanabe, Naoya Inoue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increases of microRNA let-7e in peripheral blood mononuclear cells in Hashimoto's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocr J (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1507/endocrj.EJ15-0577"}], "href": "https://doi.org/10.1507/endocrj.EJ15-0577"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26821743"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26821743"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lingshang Kong, Xiaolong Du, Nan Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of let-7e-5p contributes to endothelial progenitor cell dysfunction in deep vein thrombosis via targeting FASLG."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.thromres.2015.12.020"}], "href": "https://doi.org/10.1016/j.thromres.2015.12.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26826505"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26826505"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Graziella Curtale, Tiziana A Renzi, Massimiliano Mirolo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multi-Step Regulation of the TLR4 Pathway by the miR-125a~99b~let-7e Cluster."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2018.02037"}], "href": "https://doi.org/10.3389/fimmu.2018.02037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30245693"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30245693"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yi-Yung Hung, Ming-Kung Wu, Meng-Chang Tsai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aberrant Expression of Intracellular let-7e, miR-146a, and miR-155 Correlates with Severity of Depression in Patients with Major Depressive Disorder and Is Ameliorated after Antidepressant Treatment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells8070647"}], "href": "https://doi.org/10.3390/cells8070647"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31252530"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31252530"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yingke Zhang, Qianqian Zhang, Lian Gui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Let-7e inhibits TNF-α expression by targeting the methyl transferase EZH2 in DENV2-infected THP-1 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.26576"}], "href": "https://doi.org/10.1002/jcp.26576"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29768655"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29768655"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Zongwei Lin, Junfeng Ge, Zhe Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Let-7e modulates the inflammatory response in vascular endothelial cells through ceRNA crosstalk."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep42498"}], "href": "https://doi.org/10.1038/srep42498"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28195197"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28195197"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Katja Derkow, Rosa Rössling, Carola Schipke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct expression of the neurotoxic microRNA family let-7 in the cerebrospinal fluid of patients with Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0200602"}], "href": "https://doi.org/10.1371/journal.pone.0200602"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30011310"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30011310"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Doyel Mitra, Partha M Das, Felicia C Huynh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Jumonji/ARID1 B (JARID1B) protein promotes breast tumor cell cycle progression through epigenetic repression of microRNA let-7e."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.304865"}], "href": "https://doi.org/10.1074/jbc.M111.304865"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21969366"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21969366"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Wei Gong, Jian Zheng, Xiaobai Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of NEAT1 restrained the malignant progression of glioma stem cells by activating microRNA let-7e."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.11403"}], "href": "https://doi.org/10.18632/oncotarget.11403"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27556696"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27556696"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Jianlin Ma, Yun Zhan, Zhipeng Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZEB1 induced miR-99b/let-7e/miR-125a cluster promotes invasion and metastasis in esophageal squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2017.04.006"}], "href": "https://doi.org/10.1016/j.canlet.2017.04.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28408353"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28408353"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Cheng-Han Tsai, Liang-Ting Lin, Chung-Yih Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Over-expression of cofilin-1 suppressed growth and invasion of cancer cells is associated with up-regulation of let-7 microRNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbadis.2015.01.007"}], "href": "https://doi.org/10.1016/j.bbadis.2015.01.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25597880"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25597880"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Shufeng Xu, Lei Zheng, Liying Kang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "microRNA-let-7e in serum-derived exosomes inhibits the metastasis of non-small-cell lung cancer in a SUV39H2/LSD1/CDH1-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Gene Ther (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41417-020-00216-1"}], "href": "https://doi.org/10.1038/s41417-020-00216-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33299140"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33299140"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Zhenjun Li, Weihuo Pan, Yi Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IGF1/IGF1R and microRNA let-7e down-regulate each other and modulate proliferation and migration of colorectal cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15384101.2018.1469873"}], "href": "https://doi.org/10.1080/15384101.2018.1469873"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29886785"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29886785"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Yujia Shan, Yuejian Liu, Lifen Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-33a and let-7e inhibit human colorectal cancer progression by targeting ST8SIA1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biochem Cell Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biocel.2017.07.016"}], "href": "https://doi.org/10.1016/j.biocel.2017.07.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28751193"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28751193"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Man Xiao, Jing Cai, Liqiong Cai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Let-7e sensitizes epithelial ovarian cancer to cisplatin through repressing DNA double strand break repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Ovarian Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13048-017-0321-8"}], "href": "https://doi.org/10.1186/s13048-017-0321-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28376831"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28376831"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Man Xiao, Jianfeng Guo, Lisha Xie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Let-7e Suppresses DNA Damage Repair and Sensitizes Ovarian Cancer to Cisplatin through Targeting PARP1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-18-1369"}], "href": "https://doi.org/10.1158/1541-7786.MCR-18-1369"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31722968"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31722968"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Meysam Mosallaei, Miganoosh Simonian, Emran Esmaeilzadeh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Single nucleotide polymorphism rs10889677 in miRNAs Let-7e and Let-7f binding site of IL23R gene is a strong colorectal cancer determinant: Report and meta-analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cancergen.2019.09.003"}], "href": "https://doi.org/10.1016/j.cancergen.2019.09.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31546198"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31546198"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Christian Beyer, Anna Zampetaki, Neng-Yu Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Signature of circulating microRNAs in osteoarthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Rheum Dis (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/annrheumdis-2013-204698"}], "href": "https://doi.org/10.1136/annrheumdis-2013-204698"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24515954"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24515954"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Michal Fedorko, Jaroslav Juracek, Michal Stanik, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Detection of let-7 miRNAs in urine supernatant as potential diagnostic approach in non-metastatic clear-cell renal cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Med (Zagreb) (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.11613/BM.2017.043"}], "href": "https://doi.org/10.11613/BM.2017.043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28694731"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28694731"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Ying Li, Yu-Dong Liu, Xing-Yu Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Let-7e modulates the proliferation and the autophagy of human granulosa cells by suppressing p21 signaling pathway in polycystic ovary syndrome without hyperandrogenism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Endocrinol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mce.2021.111392"}], "href": "https://doi.org/10.1016/j.mce.2021.111392"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34246727"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34246727"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Deepak Poria, Chi Sun, Andrea Santeford, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EML1 is essential for retinal photoreceptor migration and survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-022-06571-3"}], "href": "https://doi.org/10.1038/s41598-022-06571-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35190581"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35190581"}]}]}]}