MIRLET7C

Summary

MIRLET7C (microRNA let-7c, HGNC:31480) is a microRNA gene on chromosome 21q21.1.

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 406885 — 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:31480
Approved symbol	MIRLET7C
Name	microRNA let-7c
Location	21q21.1
Locus type	RNA, micro
Status	Approved
Aliases	hsa-let-7c
Ensembl gene	ENSG00000199030
Ensembl biotype	miRNA
OMIM	612144
Entrez	406885
RNAcentral	URS0000031E12 — miRNA, 84 nt, 25 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 miRNA

ENST00000362160

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000362160 — 1 exons

Exon	Start	End
ENSE00001436923	16539828	16539911

Expression profiles

Bgee: expression breadth broad, 84 present calls, max score 91.42.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	91.42	gold quality
epididymis	UBERON:0001301	89.65	gold quality
placenta	UBERON:0001987	81.79	gold quality
calcaneal tendon	UBERON:0003701	78.86	gold quality
muscle of leg	UBERON:0001383	78.02	gold quality
blood	UBERON:0000178	76.56	gold quality
lung	UBERON:0002048	75.51	gold quality
stomach	UBERON:0000945	74.45	gold quality
islet of Langerhans	UBERON:0000006	72.83	gold quality
endometrium	UBERON:0001295	72.72	gold quality
intestine	UBERON:0000160	72.22	gold quality
monocyte	CL:0000576	71.94	gold quality
heart	UBERON:0000948	71.42	gold quality
heart left ventricle	UBERON:0002084	71.29	gold quality
kidney	UBERON:0002113	70.90	gold quality
adult mammalian kidney	UBERON:0000082	70.26	gold quality
body of pancreas	UBERON:0001150	70.03	gold quality
adrenal gland	UBERON:0002369	69.64	gold quality
liver	UBERON:0002107	69.48	gold quality
gastrocnemius	UBERON:0001388	69.16	gold quality
right adrenal gland	UBERON:0001233	69.11	gold quality
midbrain	UBERON:0001891	68.98	gold quality
substantia nigra	UBERON:0002038	68.98	gold quality
urinary bladder	UBERON:0001255	68.95	gold quality
uterus	UBERON:0000995	68.91	gold quality
left coronary artery	UBERON:0001626	68.84	gold quality
mucosa of stomach	UBERON:0001199	68.72	gold quality
colon	UBERON:0001155	67.77	gold quality
tibial artery	UBERON:0007610	67.76	gold quality
body of stomach	UBERON:0001161	67.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.31

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARA

Literature-anchored findings (GeneRIF, showing 40)

• miRNA expression pattern may serve as biomarker of human renal allograft status (PMID:19289845)
• Down-regulation of miR-let7c is associated with prostate cancer metastasis. (PMID:19372056)
• Compared to common acquired nevi, mir-125b was found to be significantly downregulated, and let-7c was significantly upregulated in atypic nevi. (PMID:21166724)
• members of the oncomir miR-17-92 cluster were upregulated, but themiR-125b/miR-99a/let-7c, miR-106b/miR-93/miR-25 and miR-212/miR-132 clusters are also coordinately regulated either by stromal cell contact alone or by CD154 (PMID:22024720)
• MicroRNA let-7c suppresses androgen receptor expression and activity via regulation of Myc expression in prostate cancer cells. (PMID:22128178)
• let-7c microRNA may play a role in regulating hepatocellular carcinoma cell differentiation. (PMID:22289550)
• miRNA overexpression inhibited influenza virus titres in infected A549 cells and inhibited M1 vRNA synthesis. (PMID:22452878)
• Results indicate that microRNA let-7c is downregulated in prostate cancer (PCa) and functions as a tumor suppressor, and is a potential therapeutic target for PCa. (PMID:22479342)
• IL-10 is a target for let-7c. (PMID:22835429)
• The miRNA let-7c expression was markedly up-regulated in ox-LDL induced apoptotic human umbilical cord vein endothelial cells (PMID:22917031)
• the effects of let-7c in acute myeloid leukemia (PMID:22964640)
• Expression of a microRNA-resistant form of IGF1R protects these cells from inhibition by the miR-99a/let7c/125b-2 cluster (PMID:23503464)
• the current study provides, for the first time, an important link between let-7c-mediated tumor growth inhibition, G1-phase cell cycle arrest of non-small cell lung cancer cells and the downregulation of HOXA1/CCND1, CDC25A and CDK2. (PMID:23534758)
• This study suggests an important role for let-7c in the molecular etiology of chemoresistant lung adenocarcinoma. (PMID:23562878)
• through regulating the expression of TRIB2 and its downstream factors, let-7c can effectively inhibit A549 cell proliferation in vitro and in vivo (PMID:23850892)
• The downregulation of let-7 by cancer-associated mesenchymal stem cells upregulates IL-6 expression. (PMID:23977098)
• ITGB3 and MAP4K3 are directly repressed by let-7c, altering the metastatic potential of lung cancer cells. (PMID:23981581)
• Results suggest that the cancer-associated rs61764370 variant exerts a biological effect not through transcriptional modulation of KRAS but rather by tuning the expression of the microRNA let-7. (PMID:24282149)
• The MiR-99a/Let-7c/miR-125b signature may improve the selection of patients with KRAS wild-type metastatic colorectal cancer as good candidates for anti-EGFR therapy. (PMID:24503111)
• Alternative promoter usage represents a regulatory mechanism of let-7c expression in different tissues. (PMID:24637061)
• It was concluded that epigenetic silencing of let-7c via Ras/NF-kappaB is involved in the acquisition of cancer stem cell-like properties and neoplastic transformation of HaCaT cells induced by arsenite. (PMID:24704393)
• Our results demonstrated that overexpressed CDK4 is an unfavorable prognostic factor which suppresses the expression of tumor suppressive-factor let-7c through p21/CCND1/CDK6/E2F1 signaling (PMID:24751144)
• Pharmacological and genetic ablation with EZH2/let-7c/PAK1 axis blunted inflammatory phenotype in M1 macrophages. (PMID:25215948)
• Let-7c overexpression inhibits dengue virus replication in human hepatoma Huh-7 cells. (PMID:25445350)
• Data indicate that combinations of microRNAs let-7c, miR-30c, miR-141, miR-375, and prostate-specific antigen (PSA) obtained better discrimination than PSA alone as noninvasive diagnostic biomarkers for screening of prostate cancer (PC). (PMID:25521481)
• Down-regulation of let-7c was associated with chemoresistance in renal cell carcinoma. (PMID:25951903)
• Results show that Let-7c levels are significantly decreased in cervical intraepithelial lesions and cancer particularly in high-grade lesions suggesting it as possible predictive biomarker for cervical intraepithelial lesion progression. (PMID:26063583)
• This study showed that increased expression of let-7c in Moyamoya Disease patients may contribute to Moyamoya Disease pathogenesis by targeting RNF213. (PMID:26070522)
• The T-allele of myotrophin rs17168525 decreases ability of let-7c to regulate translation. (PMID:26274321)
• let-7c, miR-200b, miR-222 and miR-424 target PBX3, which is necessary for the acquisition and maintenance of liver tumour-initiating cells properties. (PMID:26420065)
• Data show that the let-7c/miR-99a/miR-125b cluster controlled tumorigenesis by targeting IL-6, IL-6R and IGF1R. (PMID:26455324)
• Low expression levels of let-7c are correlated with Helicobacter pylori-related gastric carcinogenesis. (PMID:26701848)
• Study indicates that let-7c is a key regulator that inhibits fibroblasts proliferation and migration during wound healing and identifies heat shock protein 70 as a direct target of let-7c. (PMID:26923191)
• The baseline expression of let-7c was also lower by ~50% in treatment resistant depression patients compared to controls. (PMID:27483380)
• CCAT1 is upregulated in docetaxel-resistant lung adenocarcinoma cells; its oncogenic function depends on sponging of let-7c, which releases Bcl-xl, promoting the acquisition of chemoresistance and epithelial-to-mesenchymal transition phenotypes (PMID:27566568)
• Study provides evidence that IGF-1/IGF-1R/hsa-let-7c axis can control the odonto/osteogenic differentiation of IGF-1-treated stem cells from apical papilla via the regulation of JNK and p38 MAPK signaling pathways. (PMID:27833148)
• Authors report that miR-199a-5p and let-7c cooperatively and efficiently inhibit HCC cell migration and invasion by targeting the metastasis promoter MAP4K3 and MAP4K3-mediated drug sensitization. (PMID:28099144)
• Low Let-7C expression is associated with lung cancer. (PMID:28184029)
• Findings uncover a novel function of let-7 miRNAs as regulators of H2B ubiquitylation, suggesting an additional mechanism whereby these miRNAs can exert their tumor-suppressive effects. (PMID:28604753)
• 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)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mirlet7c-2	ENSDARG00000080238
danio_rerio	mirlet7c-1	ENSDARG00000081442
mus_musculus	Mirlet7c-1	ENSMUSG00000065557
rattus_norvegicus	Mirlet7c1	ENSRNOG00000035500

Paralogs (10): MIRLET7E (ENSG00000198972), MIRLET7A2 (ENSG00000198975), MIRLET7F1 (ENSG00000199072), MIRLET7D (ENSG00000199133), 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.