MIRLET7A1

Summary

MIRLET7A1 (microRNA let-7a-1, HGNC:31476) is a microRNA gene on chromosome 9q22.32.

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 406881 — 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:31476
Approved symbol	MIRLET7A1
Name	microRNA let-7a-1
Location	9q22.32
Locus type	RNA, micro
Status	Approved
Aliases	hsa-let-7a-1
Ensembl gene	ENSG00000199165
Ensembl biotype	miRNA
OMIM	605386
Entrez	406881
RNAcentral	URS00005EB5B7 — miRNA, 80 nt, 37 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 miRNA

ENST00000362295

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000362295 — 1 exons

Exon	Start	End
ENSE00001437058	94175957	94176036

Expression profiles

Bgee: expression breadth tissue_specific, 6 present calls, max score 89.24.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
caudate nucleus	UBERON:0001873	89.24	gold quality
gastrocnemius	UBERON:0001388	86.60	gold quality
tibial nerve	UBERON:0001323	77.37	gold quality
liver	UBERON:0002107	71.88	gold quality
blood	UBERON:0000178	70.53	gold quality
tibial artery	UBERON:0007610	66.34	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): MYC

Literature-anchored findings (GeneRIF, showing 40)

• suggest the involvement of let-7 miRNA in the growth of colon cancer cells (PMID:16651716)
• let-7a modulates interleukin-6-dependent STAT-3 survival signaling in malignant human cholangiocytes (PMID:17220301)
• The decreased let-7 expression is associated with C. parvum-induced up-regulation of TLR4 in infected cells. (PMID:17660297)
• Late repression of high mobility group A2 gene (HMGA2) by let-7 during cancer development correlates with the hypothesis of cancer development as a case of reverse embryogenesis. (PMID:17957144)
• Let-7-mediated repression of HMGA2 mechanism can be an important molecular event in leiomyoma growth. (PMID:18403645)
• Cdc34 is a functional target of let-7 and that let-7 induces down-regulation of Cdc34, stabilization of the Wee1 kinase, and an increased fraction of cells in G(2)/M in primary fibroblasts. (PMID:19126550)
• loss of let-7 expression induces high-mobility group A2 upregulation that represents an important mechanism in pituitary tumorigenesis and progression. (PMID:19136928)
• Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let-7 (PMID:19153603)
• Cell cycle can significantly influence the expression level of let-7a in HeLa cells. (PMID:19304520)
• The 5’ end of let-7a is critical but the 3’ end is dispensable for requirement for the microRNA ends in the formation of an active ribonucleoprotein complex. (PMID:19508234)
• Let-7 repression leads to HMGA2 overexpression in uterine leiomyosarcoma (PMID:19602040)
• Decreased expression of let-7a miRNA is associated with laryngeal cancer. (PMID:19787239)
• Src activates an inflammatory signal, and epigenetic inheritance is mediated by a positive feedback loop involving the NF-kappaB transcription factor, Lin28, Let-7 microRNA, and IL6; this regulatory circuit links inflammation to cellular transformation. (PMID:19878981)
• Data show that loss of let-7 function enhances lung tumor formation in vivo, strongly supporting the hypothesis that let-7 is a tumor suppressor. (PMID:19966857)
• the 3’UTR of E2F2 and CCND2 were directly bound to let-7a and let-7a down-regulated the expression of E2F2 and CCND2, suppressing prostate cancer cell proliferation in culture (PMID:20418948)
• found no evidence that mutations in let-7 or in binding sites of let-7 mRNA targets lead to an upregulation of RAS genes in juvenile myelomonocytic leukemia (PMID:20460640)
• These data suggest that miRNAs play an important role in the regulation of cytokine-inducible Src homology and SOCS expression in epithelial cells in response to C. parvum infection. (PMID:20486857)
• Loss of Let-7 microRNA is associated with glioblastoma. (PMID:20607356)
• hnRNP A1 and KSRP have antagonistic roles in the post-transcriptional regulation of let-7a expression. (PMID:20639884)
• abnormal epigenetic down-regulation of PRDM1 by let-7 and other microRNAs may represent an alternative mechanism of reducing normal PRDM1 function in a subset of diffuse large B cell lymphomas. (PMID:20651244)
• Let-7a may up-regulate the expression of IGFs in cancer cells, which is different from its inhibitory effects on other oncogenes (PMID:20848182)
• Data suggest that A rebalancing of the LIN28/let-7 regulatory loop could be a novel therapeutic strategy to target ALDH1+ cancer stem cells. (PMID:21045151)
• Pancreatic ductal adenocarcinoma cells repress let-7 microRNA, in part through increased TGF-beta1-mediated expression of MT1-MMP (PMID:21057545)
• we propose that PGRMC1 expression is regulated by the miRNAs let-7/miR-98 (PMID:21109987)
• Reduced let-7a is associated with gastric cancer. (PMID:21349817)
• inhibition of let-7 microRNA expression may participate in the deregulation of HMGA2 in adipocytic tumors. (PMID:21412931)
• This study suggests that repression of let-7 relieves cytokine IL-6 and IL-10 mRNAs from negative post-transcriptional control in macrophages and epithelial cells upon Salmonella infection. (PMID:21468030)
• Let-7a miRNAs were under-expressed in the blood of non-small cell lung cancer (NSCLC) patients, as well as NSCLC cells and NSCLC tissues, compared to normal controls. (PMID:21468581)
• Fas and let-7 microRNAs form a double-negative feedback loop in IFN-gamma and Fas induced apoptosis in colon carcinoma cell line HT29, which may be an important synergistic mechanism in anti-tumor immune response. (PMID:21530489)
• Let-7 may inhibit cell proliferation and be downregulated in esophageal squamous cell carcinoma, with a correlation between lower expression levels and lymph node metastasis. (PMID:21598109)
• Let-7a and miR-16 plasma levels can serve as noninvasive prognostic markers in myelodysplastic syndrome patients. (PMID:21602527)
• Let-7 microRNAs inhibit IL-13 expression (PMID:21616524)
• The tumour-suppressor miRNAs let-7 and mir-101 target MYCN and inhibit proliferation and clonogenic growth of MYCN-amplified neuroblastoma cells. (PMID:21654684)
• These results suggested that SG7011(let7T) may be a promising anticancer agent or vector to mediate the expression of therapeutic gene, broadly applicable in the treatment for HCC and other cancers where the let-7 gene is downregulated. (PMID:21814544)
• These results suggested a novel regulatory mechanism of let-7 miRNAs on ER-alpha36 mediated nongenomic estrogen signal pathways. (PMID:21826373)
• Data demonstrate that miR-107 negatively regulates the tumor suppressor miRNA let-7 via a direct interaction. (PMID:21841313)
• Direct repression of let-7a by EWS-FLI-1 participates in the tumorigenic potential of Ewing’s sarcoma family tumors cells. (PMID:21853155)
• Signalling pathway for RKIP and Let-7 regulates and predicts metastatic breast cancer. (PMID:21873975)
• Results indicate that early-stage colorectal cancer (CRC) with the KRAS-lethal-7 (let-7) miRNA complementary site (LCS6) variant have a better outcome. (PMID:21994416)
• ER-regulated hsa-let-7 microRNAs can be detected in most hyperplastic endometria, suggesting their potential utility as indicators of estrogen over-exposure. (PMID:22014978)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mirlet7a-1	ENSMUSG00000065421
rattus_norvegicus	Mirlet7a1	ENSRNOG00000035632

Paralogs (10): MIRLET7E (ENSG00000198972), MIRLET7A2 (ENSG00000198975), MIRLET7C (ENSG00000199030), MIRLET7F1 (ENSG00000199072), MIRLET7D (ENSG00000199133), MIRLET7G (ENSG00000199150), MIRLET7I (ENSG00000199179), MIRLET7F2 (ENSG00000208012), MIR98 (ENSG00000271886), MIRLET7A3 (ENSG00000283990)

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.