MIR34A

Summary

MIR34A (microRNA 34a, HGNC:31635) is a microRNA gene on chromosome 1p36.22.

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. This miRNA is a member of the highly conserved miR-34 family. This miRNA functions as a tumor suppressor and dysregulation or loss of the host gene from which this miRNA is processed is associated with cancer progression in numerous cell types.

Source: NCBI Gene 407040 — 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:31635
Approved symbol	MIR34A
Name	microRNA 34a
Location	1p36.22
Locus type	RNA, micro
Status	Approved
Aliases	hsa-mir-34a
Ensembl gene	ENSG00000284357
Ensembl biotype	miRNA
OMIM	611172
Entrez	407040
RNAcentral	URS000033F823 — miRNA, 110 nt, 7 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 miRNA

ENST00000385130

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000385130 — 1 exons

Exon	Start	End
ENSE00001500136	9151668	9151777

Expression profiles

Bgee: expression breadth broad, 23 present calls, max score 67.64.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
liver	UBERON:0002107	67.64	gold quality
gastrocnemius	UBERON:0001388	64.91	gold quality
left adrenal gland	UBERON:0001234	64.22	gold quality
transverse colon	UBERON:0001157	62.90	gold quality
left lobe of thyroid gland	UBERON:0001120	62.74	gold quality
subcutaneous adipose tissue	UBERON:0002190	62.65	gold quality
right atrium auricular region	UBERON:0006631	62.23	gold quality
vagina	UBERON:0000996	61.86	gold quality
body of pancreas	UBERON:0001150	61.73	gold quality
right hemisphere of cerebellum	UBERON:0014890	59.97	gold quality
skin of leg	UBERON:0001511	58.54	gold quality
skin of abdomen	UBERON:0001416	56.80	gold quality
nucleus accumbens	UBERON:0001882	56.18	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	55.81	gold quality
small intestine Peyer’s patch	UBERON:0003454	55.02	gold quality
putamen	UBERON:0001874	53.23	gold quality
brain	UBERON:0000955	53.14	gold quality
cerebellar hemisphere	UBERON:0002245	53.13	gold quality
minor salivary gland	UBERON:0001830	50.02	gold quality
body of stomach	UBERON:0001161	49.87	gold quality
pituitary gland	UBERON:0000007	47.69	gold quality
omental fat pad	UBERON:0010414	43.60	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	38.92	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): NFKB, NR0B2, NR1H4, RELA, TP53

Literature-anchored findings (GeneRIF, showing 40)

• miR-34a directly targets the mRNA encoding E2F3 and significantly reduces the levels of E2F3 protein in neuroblastoma cells. (PMID:17297439)
• Expression of the primary miR-34a transcript was induced after p53 activation and by DNA damage in a p53-dependent manner. (PMID:17554199)
• miR-34a functions as a potent suppressor of cell proliferation through modulation of the E2F signaling pathway (PMID:17875987)
• findings show microRNA-34a is overexpressed in various types of human cancers (PMID:17888029)
• findings show that miRNA-34a supports cell proliferation in rat oxidative stress-induced renal carcinogenesis (PMID:17888029)
• These data suggest that the effects of miR-34a on G1 cell cycle arrest are through the down-regulation of CCND1 and CDK6, which is associated with other targets of miR-34a either additively or synergistically. (PMID:18406353)
• p53-mediated mir34a, mir34b, and mir34c up-regulation and ING2 down-regulation may be involved in the senescence pathway. (PMID:18451145)
• study demonstrates one important regulatory role of miR-34a in cell growth and MYCN suppression in neuroblastoma (PMID:18504438)
• miR-34a is a tumor suppressor gene in human neuroblastoma (PMID:18505919)
• miR-34a represents a tumor suppressor gene which is inactivated by CpG methylation and subsequent transcriptional silencing in a broad range of tumors. (PMID:18719384)
• miR-34a functions as a tumor suppressor, in part, through a SIRT1-p53 pathway (PMID:18755897)
• results demonstrate that in p53-deficient human gastric cancer cells, restoration of functional miR-34 inhibits cell growth and induces chemosensitization and apoptosis, indicating that miR-34 may restore p53 function[MIRN34] (PMID:18803879)
• The expression of microRNA-34a is significantly downregulated in B-CLL patients carrying 17p13/TP53 deletions compared with patients without such deletions. (PMID:18818704)
• Reporter assays revealed that miR-34a-induced SIRT1 inhibition occurred at the transcriptional but not post-transcriptional level despite the presence of a potential miR-34a binding site within its 3’-UTR. (PMID:18834855)
• Up-regulation of miR-34a after irradiation was associated with induction of Bax and p21, but not Puma (PMID:18941118)
• miR-34a has a role in tumor migration and invasion through modulation of the c-Met signaling pathway (PMID:19006648)
• the deregulated miR expression pattern, miR-34a, miR-29 and miR-17-5p, in CLL patients with deleted and/or mutated p53 gene are closely associated to the biological subtypes of CLL (PMID:19158830)
• Knockdown of viral E6 expression in HPV16(+) and HPV18(+) cervical cancer cell lines by siRNAs leads to an increased expression of p53 and miR-34a and accumulation of miR-34a in G(0)/G(1) phase cells. (PMID:19258450)
• down regulation of miR-34a, miR-29 and miR-17-5p in aggressive CLL with TP53 abnormalities (PMID:19347736)
• miR34a-mediated inhibition of endogenous WNT1 and JAG1 expression was important for proper monocyte-derived dendritic cell differentiation (PMID:19398721)
• miR-34a functions as a tumor suppressor in RB cells and is a potential therapeutic target. (PMID:19443717)
• evidence for a role of miR-34a and miR-34b/c in the apoptotic response of normal and tumor cells (PMID:19461653)
• miR-34a contributes to megakaryocytic differentiation of K562 cells independently of p53. (PMID:19584398)
• Expression of MiR-34s was decreased in tumor samples, and MiR-34 genes underwent minimal deletions and epigenetic inactivation in osteosarcomas. (PMID:19632201)
• Chronic lymphocytic leukemia with the 17p deletion or TP53 mutation showed very low miR-34a expression. (PMID:19643983)
• During senescence, miR-34a targets the important proto-oncogene MYC and our data suggest that miR-34a thereby coordinately controls a set of cell cycle regulators (PMID:19696787)
• miR-34 may restore, at least in part, the tumor suppressing function of the p53 in p53-deficient human pancreatic cancer cells (PMID:19714243)
• a novel prognostic marker in non-small-cell lung cancer patients (PMID:19736307)
• Knockdown microRNA-34a decreased the rate of apoptosis caused by PRIMA-1 in lung cancer. (PMID:19921694)
• B-CLL cells had 4.6-fold higher miR-34a expression compared with B cells of healthy controls (PMID:20089965)
• miR-34a methylation is preferentially hypermethylated in NHL, in particular NK/T-cell lymphoma, in a tumor-specific manner. (PMID:20118199)
• Results suggest that miRNAs -26a, -34a, -145, and let-7b may modulate expression of IFN-beta, thereby influencing innate immunity from the earliest responses to viral infection. (PMID:20130213)
• Transfection of miR-34a into HepG2 cells caused suppression of cell proliferation, inhibition of cell migration and invasion. (PMID:20186752)
• miR-34a is a tumor suppressor. (PMID:20190569)
• results highlight an important regulatory role for miR-34a in the process of megakaryocytic differentiation, especially in the arrest of cell growth, which is a prerequisite for cells to enter differentiation (PMID:20299489)
• results provide evidence that miR-34a inhibits invasiveness through regulation of the Notch pathway and its downstream matrix degrading enzyme (PMID:20351093)
• Reduced miR-34a expression is associated with cervical lesions with high-risk human papillomavirus infection. (PMID:20442590)
• Studies indicate that positive feedback regulatory network based on p53 and miR-34 families play an important role in suppression of oncogenesis and deterioration. (PMID:20466628)
• Results demonstrate that miR-34a acts as a tumor suppressor in p53-mutant glioma cells U251, partially through regulating SIRT1. (PMID:20470934)
• these data suggest that miR-34a contributes to endothelial senescence through suppression of SIRT1. (PMID:20627091)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mir34a	ENSDARG00000081220
mus_musculus	Mir34a	ENSMUSG00000065493
rattus_norvegicus	Mir34a	ENSRNOG00000035623
drosophila_melanogaster	mir-34	FBGN0262459
caenorhabditis_elegans		WBGENE00003262

Paralogs (2): MIR34C (ENSG00000207562), MIR34B (ENSG00000207811)

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.