MIRLET7D

Summary

MIRLET7D (microRNA let-7d, HGNC:31481) 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 406886 — 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:31481
Approved symbol	MIRLET7D
Name	microRNA let-7d
Location	9q22.32
Locus type	RNA, micro
Status	Approved
Aliases	hsa-let-7d
Ensembl gene	ENSG00000199133
Ensembl biotype	miRNA
OMIM	612145
Entrez	406886
RNAcentral	URS000075B243 — miRNA, 87 nt, 25 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 miRNA

ENST00000362263

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000362263 — 1 exons

Exon	Start	End
ENSE00001437026	94178834	94178920

Expression profiles

Bgee: expression breadth broad, 30 present calls, max score 84.32.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
muscle of leg	UBERON:0001383	84.32	gold quality
liver	UBERON:0002107	79.46	gold quality
blood	UBERON:0000178	66.32	gold quality
ovary	UBERON:0000992	65.37	gold quality
heart left ventricle	UBERON:0002084	63.28	gold quality
bone marrow	UBERON:0002371	62.12	gold quality
epididymis	UBERON:0001301	62.05	gold quality
subcutaneous adipose tissue	UBERON:0002190	61.64	gold quality
heart	UBERON:0000948	61.24	gold quality
right lobe of liver	UBERON:0001114	60.58	gold quality
endometrium	UBERON:0001295	60.22	gold quality
uterus	UBERON:0000995	60.21	gold quality
right atrium auricular region	UBERON:0006631	59.44	gold quality
caudate nucleus	UBERON:0001873	55.91	gold quality
renal glomerulus	UBERON:0000074	55.78	silver quality
skin of leg	UBERON:0001511	55.77	gold quality
midbrain	UBERON:0001891	55.52	gold quality
substantia nigra	UBERON:0002038	55.51	gold quality
pituitary gland	UBERON:0000007	55.39	gold quality
anterior cingulate cortex	UBERON:0009835	54.27	gold quality
thyroid gland	UBERON:0002046	53.91	silver quality
spleen	UBERON:0002106	53.29	silver quality
prostate gland	UBERON:0002367	52.79	silver quality
testis	UBERON:0000473	52.17	silver quality
skin of abdomen	UBERON:0001416	52.07	gold quality
tibial artery	UBERON:0007610	51.82	gold quality
placenta	UBERON:0001987	51.47	gold quality
islet of Langerhans	UBERON:0000006	51.16	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	49.53	gold quality
putamen	UBERON:0001874	40.44	silver 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): SMAD3

Literature-anchored findings (GeneRIF, showing 40)

• Data suggest that miR-Let-7d participates in the finely tuned regulation of iron metabolism by targeting DMT1-IRE isoform in erythroid cells. (PMID:20410187)
• Data show that the let-7 (let-7d and let-7g) target IMP-1 stabilizes the mRNA of MDR1. (PMID:21618519)
• Results show that let-7d negatively modulates EMT expression and also plays a role in regulating chemo-resistant ability in oral cancer. (PMID:21725603)
• Data indicate that miR-181b, miR-153, miR-145, miR-137, and let-7d were significantly upregulated after treatment with Olea europaea leaf extract (OLE) and temozolomide (TMZ). (PMID:22722712)
• These results suggest that let-7d may suppress renal cell carcinoma growth, metastasis, and tumor macrophage infiltration at least partially through targeting COL3A1 and CCL7. (PMID:25193015)
• Higher circulation level of miRNA let-7d was significantly associated with attention-deficit/hyperactivity disorder. A significantly higher rate of clinical improvement was noted in subjects with low level of circulating miRNA let-7d than those with a high level. (PMID:25724585)
• The combination of serum let-7b, 7d, and 7f levels during the proliferative phase may serve as a diagnostic marker for endometriosis. (PMID:25772772)
• genetic association study in population in Beijing, China: Data suggest 3 SNPs in mirnlet7 (rs10993081 mirnlet7d, rs10877887 mirnlet7i, rs17276588 mirnlet7f) on chromosomes 9, 12, and x are associated with metabolic syndrome in the population studied. (PMID:26178671)
• Data suggest that promoter activity/expression of miRNA let-7 gene cluster in skeletal muscle satellite cells are up-regulated in response to glucose, TNFa (tumor necrosis factor-alpha), and caffeine (but not insulin). (PMID:26378151)
• Let-7d has both tumor suppressor and oncogenic functions in osteosarcoma-derived tumor stem cells. (PMID:26679758)
• The study deciphered the essential role of Lin28B in the pathogenesis of epithelial-mesenchymal transition in idiopathic pulmonary fibrosis, and unraveled a novel mechanism that miR-26a is a modulator of let-7d. (PMID:26787543)
• Results revealed for the first time that glioblastoma exhibited differential MYC mediated transcriptional inhibition on MC-let-7a-1~let-7d due to the defective MYC/E-box3 binding. (PMID:27409345)
• There is strong evidence for small nerve fiber impairment in a subgroup of patients suffering from FMS, which is possibly linked to altered MIRLET7D expression and concurrent decreased cutaneous IGF-1R signaling. (PMID:27429177)
• The let7dinduced Akt1 inhibition contributed to tumor repression, with similar results to those obtained with Akt inhibitors. Furthermore, it was identified that the inhibition of Wnt1 is critical for the functioning of let7d, and that addition of recombinant Wnt1 abolished the effects of let7d on sensitization to radiotherapy in triple negative breast cancer. (PMID:27574028)
• miR-25-3p and let-7d-5p in plasma were differentially expressed between Acute exacerbation of idiopathic pulmonary fibrosis and stable idiopathic pulmonary fibrosis (PMID:27881157)
• results indicated that the level of let-7d expression is an important factor for cell response to irradiation and chemotherapeutics (PMID:28665983)
• Concentrations of all let-7 miRNAs let-7a, let-7b, let-7c, let-7d, let-7e and let-7g were significantly higher in urine samples obtained from renal cell carcinoma (RCC) patients compared to healthy controls. (PMID:28694731)
• In the risk study, the let-7i rs10877887 and let-7a-1/let-7f-1/let-7d rs13293512 were shown no significant association for the overall cancer risk. In the stratified analysis, the rs10877887 variant genotype was significantly associated with a decreased cancer risk in head and neck cancer. (PMID:29717029)
• Results revealed that LET7D expression was downregulated in colon cancer (CC) compared with normal tissues. Its overexpression suppresses CC cell proliferation through CST1/p65. (PMID:29845224)
• These findings provide novel insights into molecular mechanism of let-7d and Jab1 in tumor development and progression of breast cancer, and thus let-7d/Jab1 are novel potential therapeutic targets for breast cancer patients. (PMID:29975923)
• Results demonstrated that the expression of let7d tissues was significantly reduced in ovarian cancer (OC) tumors and cell lines. Let7d represses OC cell lines viability by targeting HMGA1. (PMID:30816441)
• Study shows that reduced levels of miRNA lethal 7d in idiopathic pulmonary fibrosis (IPF) compromise epigenetic gene silencing mediated by the ribonucleoprotein complex MiCEE. Hyperactive EP300 reduces nuclear HDAC1 and interferes with MiCEE function in IPF. (PMID:31110176)
• the inhibitory roles of let-7d on the proliferation, migration, and tubulogenesis of endothelial cells, are reported. (PMID:31435814)
• MiR-let-7d-3p regulates IL-17 expression through targeting AKT1/mTOR signaling in CD4(+) T cells. (PMID:31768762)
• HMGA2 and KRAS could be translationally downregulated by the hsa-let-7d-3p, and the loss of hsa-let-7d-3p expression led to the progression of EOC related to the tumorigenesis, invasion, and metastasis. (PMID:31898667)
• Low let-7d exosomes from pulmonary vascular endothelial cells drive lung pericyte fibrosis through the TGFbetaRI/FoxM1/Smad/beta-catenin pathway. (PMID:33179861)
• HMGA2-induced epithelial-mesenchymal transition is reversed by let-7d in intrauterine adhesions. (PMID:33237328)
• Let-7d inhibits intratumoral macrophage M2 polarization and subsequent tumor angiogenesis by targeting IL-13 and IL-10. (PMID:33237349)
• Let-7d and miR-185 Impede Epithelial-Mesenchymal Transition by Downregulating Rab25 in Breast Cancer. (PMID:33507713)
• Downregulation of exosomal let-7d and miR-16 in idiopathic pulmonary fibrosis. (PMID:34088304)
• Induction of microRNA hsa-let-7d-5p, and repression of HMGA2, contribute protection against lipid accumulation in macrophage ‘foam’ cells. (PMID:34274506)
• The Role of microRNA Let-7d in Female Malignancies and Diseases of the Female Reproductive Tract. (PMID:34298978)
• Overexpression of let-7d explains down-regulated KDM3A and ENO2 in the pathogenesis of preeclampsia. (PMID:34350711)
• MiRNA Let-7a and Let-7d Are Induced by Globotriaosylceramide via NF-kB Activation in Fabry Disease. (PMID:34440358)
• MiR-let-7d-3p inhibits granulosa cell proliferation by targeting TLR4 in polycystic ovary syndrome. (PMID:34655744)
• Evaluation of hsa-let-7d-5p, hsa-let-7g-5p and hsa-miR-15b-5p plasma levels in patients with Alzheimer’s disease. (PMID:34955516)
• Blood circulating miR-28-5p and let-7d-5p associate with premature ageing in Down syndrome. (PMID:35780970)
• Maternal expression of miR-let-7d-3p and miR-451a during gestation influences the neuropsychomotor development of 90 days old babies: “Pregnancy care, healthy baby” study. (PMID:36587497)
• Increased let-7d-5p in non-alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosis. (PMID:37057737)
• High glucose promotes atherosclerosis by regulating miRNA let7d-5p level. (PMID:38483136)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mirlet7a-5	ENSDARG00000080890
danio_rerio	mirlet7a-6	ENSDARG00000082173
mus_musculus	Mirlet7d	ENSMUSG00000065453
rattus_norvegicus	Mirlet7d	ENSRNOG00000035594
drosophila_melanogaster	mir-let7	FBGN0262406

Paralogs (10): MIRLET7E (ENSG00000198972), MIRLET7A2 (ENSG00000198975), MIRLET7C (ENSG00000199030), MIRLET7F1 (ENSG00000199072), MIRLET7G (ENSG00000199150), MIRLET7A1 (ENSG00000199165), 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.