MIR449A

Summary

MIR449A (microRNA 449a, HGNC:27645) is a microRNA gene on chromosome 5q11.2.

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 554213 — 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:27645
Approved symbol	MIR449A
Name	microRNA 449a
Location	5q11.2
Locus type	RNA, micro
Status	Approved
Aliases	hsa-mir-449, hsa-mir-449a
Ensembl gene	ENSG00000198983
Ensembl biotype	miRNA
OMIM	613131
Entrez	554213
RNAcentral	URS00006A0D74 — miRNA, 91 nt, 2 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 miRNA

ENST00000362113

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000362113 — 1 exons

Exon	Start	End
ENSE00001436876	55170532	55170622

Expression profiles

Bgee: expression breadth broad, 25 present calls, max score 82.77.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.77	gold quality
calcaneal tendon	UBERON:0003701	78.42	gold quality
intestine	UBERON:0000160	76.28	gold quality
blood	UBERON:0000178	75.82	gold quality
heart	UBERON:0000948	71.55	gold quality
monocyte	CL:0000576	71.17	gold quality
thoracic mammary gland	UBERON:0005200	70.25	gold quality
endometrium	UBERON:0001295	69.86	gold quality
ascending aorta	UBERON:0001496	69.66	gold quality
gastrocnemius	UBERON:0001388	67.75	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	67.51	gold quality
skin of abdomen	UBERON:0001416	66.00	gold quality
left ovary	UBERON:0002119	65.86	gold quality
stomach	UBERON:0000945	64.68	gold quality
subcutaneous adipose tissue	UBERON:0002190	64.41	gold quality
omental fat pad	UBERON:0010414	64.05	gold quality
lower esophagus muscularis layer	UBERON:0035833	64.02	gold quality
tibial nerve	UBERON:0001323	63.42	gold quality
Ammon’s horn	UBERON:0001954	62.77	gold quality
myometrium	UBERON:0001296	61.56	gold quality
left lobe of thyroid gland	UBERON:0001120	59.71	gold quality
thyroid gland	UBERON:0002046	59.71	gold quality
cerebellar hemisphere	UBERON:0002245	58.02	gold quality
testis	UBERON:0000473	41.93	gold quality
left testis	UBERON:0004533	41.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RUNX1

Literature-anchored findings (GeneRIF, showing 40)

• miR-449a targets HDAC-1 and induces growth arrest in prostate cancer. (PMID:19252524)
• Data suggest that miR-449a and b provide a twofold safety mechanism to avoid excessive E2F1-induced proliferation by cell cycle arrest and by apoptosis. (PMID:19960022)
• Data describe a novel hypoxia-dependent mechanism involving decreased miRNA-449a/b, hypoxia-induced amplification of targeted SERPINE1 (PAI-1) and its overexpression in tissues showing a hypoxic environment. (PMID:20356416)
• Data indicate that miR-449a is a miRNA component of the Rb pathway and its tumor suppressor-like effects, in part, depends on Rb status in prostate cancer cells. (PMID:20948989)
• miR-449 induces senescence and apoptosis by activating the p53 pathway. (PMID:21418558)
• Notch1 and its ligand Delta-like 1(DLL1) are miR-449 bona fide targets (PMID:21602795)
• miR-449 strongly accumulated in multiciliated cells in human airway epithelium and Xenopus laevis embryonic epidermis, where it triggered centriole multiplication and multiciliogenesis by directly repressing the Delta/Notch pathway. [review] (PMID:21857154)
• high miR-449a levels targeted and reduced both NOTCH1 and KLF4. (PMID:22194996)
• Results suggest a tumor-suppressive role for miR-449a in human bladder cancer. (PMID:22266187)
• miR-449a, recognizes and regulates the expression of LEF-1 in a dose-dependent and sequence-specific manner. (PMID:22769578)
• miRNA-449a plays an important role in modulating expression of YKL40 through targeting the components of the NOTCH signaling pathway following hepatitis C virus infection. (PMID:23226395)
• miR-449a post-transcriptionally regulates expression of HNF-4alpha, and affect HNF-4alpha binding and transactivation of its target genes by selective targeting of the HNF-4A 3’-UTR. (PMID:23298640)
• Overexpression of miR-449a in CL1-0 cells effectively increased irradiation-induced DNA damage and apoptosis, altered the cell cycle distribution and eventually led to sensitization of CL1-0 to irradiation. (PMID:23614048)
• Data show that the expression of miR-449a was reciprocally correlated with c-Met in non-small cell lung cancer (NSCLC) tissues. (PMID:23734217)
• This study suggests that MIR449A and MIR449B could serve as viable therapeutic targets for retinoblastoma treatment. (PMID:24120948)
• miR-449a could modulate cell cycle and apoptosis through regulating cyclin D1 and BCL2 expression in gastric cancer cells. (PMID:24248414)
• Hepatitis C virus-induced changes in miRNA-449a and miRNA-107 regulate CCL2 expression by activation of the IL-6-mediated signaling cascade by targeting components of the interleukin-6 receptor complex. (PMID:24429361)
• ANRIL-mediated growth promotion is in part due to epigenetic repression of miR-99a/miR-449a in gastric cancer (PMID:24810364)
• Results suggest that miR-449a may act as a tumor suppressor by targeting CDC25A in endometrial cancer. (PMID:24993091)
• MicroRNA-449a reduces cell survival and enhances cisplatin-induced cytotoxicity via downregulation of NOTCH1 in ovarian cancer cells. (PMID:25179844)
• Expression of miR-449 was significantly lower in uterine clear cell carcinomas than in endometrioid carcinomas. (PMID:25238166)
• The tumor suppression role of microRNA-449a could be due to its promotion of tumor cell proliferation and its inhibition of tumor cell apoptosis. (PMID:25424357)
• Myc-associated zinc-finger protein (MAZ) was identified as a direct target of miR-449a, mediating the tumor-suppressive effects. (PMID:25487955)
• These results suggest the critical role of the differentiation-inducing function of miR-449a in determining neuroblastoma progression. (PMID:25760387)
• Loss of MicroRNA-449a expression is associated with metastasis in lung cancer. (PMID:25818739)
• The tumor suppressor functions of miR-449a in GC involve the inhibition of cell proliferation, induction of G0/G1 arrest and apoptosis by directly targeting E2F3. (PMID:25871967)
• Loss of miRNA-449a expression is associated with osteosarcoma. (PMID:26002578)
• Low miR449a expression is associated with liver cancer. (PMID:26375440)
• miR-34/449 promote the assembly of an apical actin network, required for proper basal bodies anchoring during multiciliogenesis. (PMID:26381333)
• Our data highlight an important role of miR-449a in the molecular etiology of HCC, and implicate the potential application of miR-449a in cancer therapy. (PMID:26471185)
• The expression of microRNA-449a is low in patients with glioma, which may inhibit the proliferation of glioma and promote its cell apoptosis via affecting the expression of PKCalpha. (PMID:26502848)
• By targeting genes involved in controlling pRb/E2F1 activity, miR-449a regulates cell cycle progression and apoptosis and consequently enhances the radiosensitivity of PC-3 cells. Thus, miR-449a, as a miRNA component of the Rb pathway, promotes the radiosensitivity of PC-3 cells through regulating pRb/E2F1. (PMID:26520443)
• that miR-449a suppressed Flot2 expression results in decreased cell invasion through repressing TGF-beta-mediated-epithelial-mesenchymal transition (PMID:26576674)
• our findings suggest that miR-449a rs112310158 is a genetic risk factor for Gastric cancer (PMID:26722545)
• Findings define an oncogenic function of miR-449a in human breast cancer, and highlight the importance of this pathway in driving aggressive behaviour. (PMID:26934316)
• We found that pre-miR-29c or miR-29c mimics significantly increases the expression level of miR-34c and miR-449a. We further found DNA methyltransferase 3a and 3b are the target gene of miR-29c (PMID:26975503)
• Our data suggest that attenuation of miR-449a promotes the invasive phenotype of the ERG-positive prostate cancer in part by inducing the expression of SIRT1 in prostate cancer cells. (PMID:26988912)
• The results indicated that epigenetically regulated miR-449a targets CREB5 to increase FXRalpha expression, thereby promoting HBV replication and gene expression. Our findings provide a new understanding of the role of miRNAs in HBV replication (PMID:27138288)
• By establishing c-Myc as a direct target of miR-449a, the authors revealed that miR-449a enhanced radiosensitivity by repressing c-Myc expression in LNCaP prostate cancer cells. (PMID:27250340)
• Expression of miR-449a was down-regulated in most of the MB samples as compared with normal human cerebellum, but expression levels were relatively high in the WNT group in this cohort. (PMID:27406588)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mir449a	ENSMUSG00000065575
rattus_norvegicus	Mir449a	ENSRNOG00000035622

Paralogs (1): MIR449B (ENSG00000207728)

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.