MIRLET7A3

Summary

MIRLET7A3 (microRNA let-7a-3, HGNC:31478) is a microRNA gene on chromosome 22q13.31.

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.

Source: NCBI Gene 406883 — RefSeq curated summary.

At a glance

• Gene type: non-coding (miRNA) — no protein product; not a drug target. Variant/disease associations are omitted (they would be positional, from an overlapping protein-coding gene).

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31478
Approved symbol	MIRLET7A3
Name	microRNA let-7a-3
Location	22q13.31
Locus type	RNA, micro
Status	Approved
Aliases	hsa-let-7a-3
Ensembl gene	ENSG00000283990
Ensembl biotype	miRNA
OMIM	612143
Entrez	406883
RNAcentral	URS00004BC34C — miRNA, 74 nt, 23 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 miRNA

ENST00000362116

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000362116 — 1 exons

Exon	Start	End
ENSE00001436879	46112749	46112822

Expression profiles

Bgee: expression breadth broad, 17 present calls, max score 73.39.

Top tissues by expression

17 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	73.39	gold quality
tibial artery	UBERON:0007610	68.37	gold quality
body of pancreas	UBERON:0001150	63.57	gold quality
substantia nigra	UBERON:0002038	63.55	gold quality
tibial nerve	UBERON:0001323	60.49	gold quality
right frontal lobe	UBERON:0002810	60.43	gold quality
nucleus accumbens	UBERON:0001882	58.64	gold quality
skin of abdomen	UBERON:0001416	56.80	gold quality
esophagus mucosa	UBERON:0002469	56.35	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	55.27	gold quality
blood	UBERON:0000178	52.78	silver quality
skin of leg	UBERON:0001511	52.04	gold quality
subcutaneous adipose tissue	UBERON:0002190	50.86	gold quality
amygdala	UBERON:0001876	50.28	gold quality
caudate nucleus	UBERON:0001873	43.27	gold quality
pituitary gland	UBERON:0000007	39.59	silver quality
left testis	UBERON:0004533	35.83	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB

Literature-anchored findings (GeneRIF, showing 26)

• let-7a-3 gene is methylated and the methylation may affect IGF-II expression and the survival of ovarian cancer patients. (PMID:17974952)
• pri-let-7 has a direct function in target repression in the absence of properly processed mature let-7, and let-7a-3 pri-miRNA can directly interact with target mRNAs. (PMID:20808284)
• The results demonstrated that lentiviral vector was capable of upregulating let-7a, resulting in impressive anticancer effects. It offers a powerful new strategy for the development of novel therapeutic interventions to treat human gastric carcinomas (PMID:20809749)
• While the levels of the endogenous primary let-7a and let-7b transcript were induced in response to NF-kappaB overexpression in 293T cells, the levels of fully processed, mature let-7a and let-7b miRNAs did not increase (PMID:22348059)
• Study uncovers a first example of a vertebrate protein factor, Argonaute-3, specifically affecting the guide-to-passenger-strand ratio of the miRNA let-7a. A multi-layered mechanism for the observed impact of Ago3 on the let-7a-3p passenger strand expression and activity is proposed. (PMID:24100239)
• let-7a-3 overexpression is a common event and is associated with poor clinical outcome in acute myeloid leukemia. (PMID:24138945)
• Reduction of let-7a3/let-7b miRNA may be one of mechanisms leading to overexpression of HMGA2 in AT/RT tissues. (PMID:24423609)
• let-7a-3 methylation is a positive prognosticator for acute myeloid leukemia patients with hypomethylated CEBPA. (PMID:24703161)
• Results show that microRNAs Let-7a and miR-335 expression levels were significantly downregulated in the tumors of patients with a BRCA mutation and correlated with tumor prognosis. (PMID:24942235)
• Results show that LOX-1 is a target of let- 7a and let-7b, and they inhibit the expression of LOX-1 by targeting its 3’-UTR. (PMID:25247304)
• overexpression of Lin28 can suppress the biological behavior of gastric cancer in vitro, and let-7 miRNA may play an important role in the process (PMID:25515921)
• Results show evidence that let-7a expression in osteosarcoma (OS) cells is significantly reduced and inversely correlated with E2F2 expression levels and that let-7a plays an important role in OS cell proliferation and tumorigenesis by targeting E2F2. (PMID:25647078)
• Plasma miR-20a and let-7a levels are significantly altered in patients with ESCC and can be used as potential biomarkers in the diagnosis of esophageal squamous cell carcinoma. (PMID:25914476)
• Promoter hypermethylation and down-expression of let-7a-3 may play a role in DN by targeting UHRF1. (PMID:26049093)
• let-7a-3 hypomethylation is associated with favorable and intermediate karyotypes but not a prognostic predictor for acute myeloid leukemia patients (PMID:26227220)
• Our current findings identify a regulatory network of miR let-7a-USP35-ABIN-2 pathway, which may serve as potential therapeutic targets to help us control the human cancer progression (PMID:26348204)
• let-7 is a tumor suppressor that negatively regulates RAS, also in Ewing Sarcoma, and HIF-1alpha may contribute to the aggressive metastatic behavior of Ewing Sarcoma (PMID:26393682)
• single let-7 family member, human let-7a-3 escapes LIN28-mediated regulation. (PMID:26440890)
• let-7a-3 hypomethylation was an independent prognostic risk factor in cohorts of MDS patients with lower-risk disease. Our study suggested that let-7a-3 hypomethylation may predict poor outcome in MDS. (PMID:27244225)
• Let-7a inhibition by HBV mRNAs resulted in enhanced HCC cell colony formation and tumor growth, providing evidence of the oncogenic potential of HBV mRNAs. (PMID:27693636)
• Expression of let-7a-5p in pneumoconiosis is downregulated, while reduced let-7a-5p corresponds to high expression of BCL2L1 and poor survival of lung adenocarcinoma patients. (PMID:30497474)
• Inhibition effect of exosomes-mediated Let-7a on the development and metastasis of triple negative breast cancer by down-regulating the expression of c-Myc. (PMID:31298382)
• Study provides evidence that let-7a miRNA positively regulates translational readthrough of AGO1. (PMID:31330067)
• Salivary miR-let-7a-5p and miR-3928 were significantly down regulated in saliva of head and neck squamous cell carcinoma patients, and have the potential to be novel non-invasive biomarkers for early detection and prognosis head and neck squamous cell carcinoma. (PMID:32208417)
• Let-7a-5p represses proliferation, migration, invasion and epithelial-mesenchymal transition by targeting Smad2 in TGF-b2-induced human lens epithelial cells. (PMID:32345785)
• Predictive Value of let-7a for Cancer Cell Repopulation between Chemotherapy and Long-Term Survival: A Prospective Study. (PMID:34686505)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dre-let-7e	ENSDARG00000081975
danio_rerio		ENSDARG00000082908
mus_musculus	Mirlet7c-2	ENSMUSG00000065608
rattus_norvegicus	Mirlet7c2	ENSRNOG00000035461

Paralogs (10): MIRLET7E (ENSG00000198972), MIRLET7A2 (ENSG00000198975), MIRLET7C (ENSG00000199030), MIRLET7F1 (ENSG00000199072), MIRLET7D (ENSG00000199133), MIRLET7G (ENSG00000199150), MIRLET7A1 (ENSG00000199165), MIRLET7I (ENSG00000199179), MIRLET7F2 (ENSG00000208012), MIR98 (ENSG00000271886)

Protein

Non-coding RNA — no protein product; not a drug target.

Function

No curated pathway, Gene-Ontology, or interaction data.

Disease & clinical

No curated disease, variant, or cancer-driver associations.

Drugs & pharmacology

No drug or pharmacology data — not an established drug target.