MIRLET7A3 Gene

HGNC Family Non-coding RNAs
Name microRNA let-7a-3
Description microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]
Summary
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In epithelial ovarian cancer, for instance, methylation of the MIRLET7A3 promoter is detected in a significant fraction of patients and is associated with modulation of key growth‐regulatory factors—its methylation correlates inversely with insulin‐like growth factor‐II (IGF‐II) and directly with insulin‐like growth factor binding protein‑3 (IGFBP‑3) expression, ultimately linking its epigenetic status to improved overall survival outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, structural features intrinsic to the MIRLET7A3 transcript critically influence its function. Detailed analyses have demonstrated that the primary transcript (pri‑let‑7a‑3) itself can directly repress target mRNAs through specific loop nucleotide elements, underscoring an activity independent from its mature form."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, transcriptional regulation studies of the MIRLET7A3/let‑7b cluster reveal that promoter responsiveness to NF‑κB can induce primary transcript expression; however, subsequent maturation to the active miRNA may be curtailed by concomitant induction of maturation inhibitors such as Lin‑28B."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Intriguingly, structural elements of the MIRLET7A3 precursor, including its loop region, render it refractory to binding by LIN28 proteins—a feature that distinguishes it from other let‑7 family members and permits its processing independent of LIN28‐mediated blockade."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond ovarian cancer, aberrant regulation of MIRLET7A3 has been implicated in other pathologies. In diabetic nephropathy, the MIRLET7A3 gene—uniquely endowed with a promoter‐associated CpG island among let‑7a homologues—undergoes hypermethylation that leads to its downregulation, contributing to dysregulation of methylation‐related effector genes such as UHRF1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In the hematopoietic compartment, overexpression of MIRLET7A3 in acute myeloid leukemia (AML) and hypomethylation in myelodysplastic syndrome (MDS) have been reported; notably in AML, elevated MIRLET7A3 levels are linked to poorer relapse‐free and overall survival after complete remission"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", while MDS patients exhibiting promoter hypomethylation of MIRLET7A3 experience adverse prognostic outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lingeng Lu, Dionyssios Katsaros, Irene A Rigault de la Longrais, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypermethylation of let-7a-3 in epithelial ovarian cancer is associated with low insulin-like growth factor-II expression and favorable prognosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-07-2544"}], "href": "https://doi.org/10.1158/0008-5472.CAN-07-2544"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17974952"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17974952"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Robin Deis Trujillo, Si-Biao Yue, Yujie Tang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The potential functions of primary microRNAs in target recognition and repression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2010.208"}], "href": "https://doi.org/10.1038/emboj.2010.208"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20808284"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20808284"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "David J Wang, Aster Legesse-Miller, Elizabeth L Johnson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of the let-7a-3 promoter by NF-κB."}]}, {"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.0031240"}], "href": "https://doi.org/10.1371/journal.pone.0031240"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22348059"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22348059"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Robinson Triboulet, Mehdi Pirouz, Richard I Gregory "}, {"type": "b", "children": [{"type": "t", "text": "A Single Let-7 MicroRNA Bypasses LIN28-Mediated Repression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2015.08.086"}], "href": "https://doi.org/10.1016/j.celrep.2015.08.086"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26440890"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26440890"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Rui Peng, Handeng Liu, Huimin Peng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Promoter hypermethylation of let-7a-3 is relevant to its down-expression in diabetic nephropathy by targeting UHRF1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2015.05.073"}], "href": "https://doi.org/10.1016/j.gene.2015.05.073"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26049093"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26049093"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yun Li, Jiang Lin, Jing Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpressed let-7a-3 is associated with poor outcome in acute myeloid leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leuk Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.leukres.2013.09.022"}], "href": "https://doi.org/10.1016/j.leukres.2013.09.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24138945"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24138945"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "De-Hong Wu, Dong-Ming Yao, Lei Yang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Let-7a-3 hypomethylation is associated with favorable/intermediate karyotypes but not with survival in acute myeloid leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13277-015-3734-2"}], "href": "https://doi.org/10.1007/s13277-015-3734-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26227220"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26227220"}]}]}]}
Synonyms LET7A3, LET-7A-3, MIRNLET7A3
NCBI Gene ID 406883
API
Download Associations
Predicted Functions View MIRLET7A3's ARCHS4 Predicted Functions.
Co-expressed Genes View MIRLET7A3's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View MIRLET7A3's ARCHS4 Predicted Functions.

Functional Associations

MIRLET7A3 has 520 functional associations with biological entities spanning 5 categories (molecular profile, disease, phenotype or trait, functional term, phrase or reference, cell line, cell type or tissue, gene, protein or microRNA) extracted from 17 datasets.

Click the + buttons to view associations for MIRLET7A3 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of MIRLET7A3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
ChEA Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of MIRLET7A3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of MIRLET7A3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
COSMIC Cell Line Gene CNV Profiles cell lines with high or low copy number of MIRLET7A3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores diseases co-occuring with MIRLET7A3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
ENCODE Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at MIRLET7A3 gene from the ENCODE Histone Modification Site Profiles dataset.
ENCODE Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of MIRLET7A3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of MIRLET7A3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
GAD Gene-Disease Associations diseases associated with MIRLET7A3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with MIRLET7A3 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
GeneSigDB Published Gene Signatures PubMedIDs of publications reporting gene signatures containing MIRLET7A3 from the GeneSigDB Published Gene Signatures dataset.
HuGE Navigator Gene-Phenotype Associations phenotypes associated with MIRLET7A3 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of MIRLET7A3 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of MIRLET7A3 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
Roadmap Epigenomics Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at MIRLET7A3 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with MIRLET7A3 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.
WikiPathways Pathways 2014 pathways involving MIRLET7A3 protein from the Wikipathways Pathways 2014 dataset.