MIR221

Summary

MIR221 (microRNA 221, HGNC:31601) is a microRNA gene on chromosome Xp11.3.

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 407006 — 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:31601
Approved symbol	MIR221
Name	microRNA 221
Location	Xp11.3
Locus type	RNA, micro
Status	Approved
Aliases	hsa-mir-221
Ensembl gene	ENSG00000207870
Ensembl biotype	miRNA
OMIM	300568
Entrez	407006
RNAcentral	URS0000245997 — miRNA, 110 nt, 16 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 miRNA

ENST00000385135

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000385135 — 1 exons

Exon	Start	End
ENSE00001500141	45746157	45746266

Expression profiles

Bgee: expression breadth ubiquitous, 114 present calls, max score 99.54.

Top tissues by expression

114 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	99.54	gold quality
bone marrow	UBERON:0002371	95.88	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.58	gold quality
left uterine tube	UBERON:0001303	92.97	gold quality
right uterine tube	UBERON:0001302	91.05	gold quality
ectocervix	UBERON:0012249	90.53	gold quality
body of uterus	UBERON:0009853	89.69	gold quality
vagina	UBERON:0000996	89.34	gold quality
smooth muscle tissue	UBERON:0001135	88.85	gold quality
skin of abdomen	UBERON:0001416	88.28	gold quality
right ovary	UBERON:0002118	88.07	gold quality
left ovary	UBERON:0002119	87.89	gold quality
esophagus mucosa	UBERON:0002469	87.74	gold quality
right lung	UBERON:0002167	87.56	gold quality
prostate gland	UBERON:0002367	87.44	gold quality
ovary	UBERON:0000992	87.05	gold quality
myometrium	UBERON:0001296	86.90	gold quality
zone of skin	UBERON:0000014	86.76	gold quality
lung	UBERON:0002048	86.58	gold quality
minor salivary gland	UBERON:0001830	86.45	gold quality
upper lobe of left lung	UBERON:0008952	86.42	gold quality
omental fat pad	UBERON:0010414	86.18	gold quality
saliva-secreting gland	UBERON:0001044	85.95	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.77	gold quality
skin of leg	UBERON:0001511	85.74	gold quality
uterus	UBERON:0000995	85.51	gold quality
urinary bladder	UBERON:0001255	85.30	gold quality
descending thoracic aorta	UBERON:0002345	85.25	gold quality
small intestine	UBERON:0002108	85.07	gold quality
right coronary artery	UBERON:0001625	85.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.31

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SNAI2, STAT1

Literature-anchored findings (GeneRIF, showing 40)

• miR-221 is upregulated in papillary thyroid carcinoma; its function is impaired by SNP within its target cKIT (PMID:16365291)
• R-221/222 can be regarded as a new family of oncogenes, directly targeting the tumor suppressor p27(Kip1), and their overexpression might be contribute to the oncogenesis and progression of prostate carcinoma through p27(Kip1) down-regulation (PMID:17569667)
• Data show that p27(Kip1) is a direct target for microRNAs 221 and 222, and suggest a role for these microRNAs in promoting the aggressive growth of glioblastoma. (PMID:17721077)
• miR-221 and miR-222 are endogenous regulators of p27(Kip1) protein expression, and thereby, the cell cycle. (PMID:17914108)
• up-regulation of miR-221 expression is an accurate way to differentiate leiomyosarcoma from benign metastasizing leiomyoma. (PMID:18382364)
• miR-221 has an oncogenic function in hepatocarcinogenesis by targeting CDKN1B/p27 and CDKN1C/p57, hence promoting proliferation by controlling cell-cycle inhibitors. (PMID:18521080)
• MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1 (PMID:18708351)
• in glioma & glioblastoma multiforme, selective upregulation of miRNA-221 & down-regulation of a miRNA-221 mRNA target encoding BIRC1 were observed; expression of BIRC5 & caspase-3 were found to be significantly up-regulated, particularly in stage IV GBM (PMID:18759060)
• miR-221 is transcriptionally induced upon PDGF treatment in primary vSMCs, leading to down-regulation of the targets c-Kit and p27Kip1. Down-regulation of p27Kip1 by miR-221 is critical for PDGF-mediated induction of cell proliferation (PMID:19088079)
• Modulating miR-221/222 levels may have a therapeutic potential in prostate carcinoma. (PMID:19107213)
• Roles are shown for transgenic microRNA-221-22 in regulating cell cycle checkpoints in mast cells; overexpression of transgenic microRNA-221-222 in a model mast cell line perturbs cell morphology and cell cycle regulation without altering viability. (PMID:19109175)
• mir-221 can directly interact with c-kit 3’UTR and inhibit cKit protein translation. (PMID:19126397)
• higher levels of miRNA-221 were found in high-grade gliomas (PMID:19159078)
• Under hyperglycemic conditions, miR-221 is induced in HUVECs, which consequently triggers inhibition of c-kit and impairment of HUVECs migration. (PMID:19351599)
• Data suggest the involvement of miR-221 and miR-222 in the development or maintenance of the castration resistant prostate cancer phenotype. (PMID:19351832)
• Co-suppression of miR-221/222 cluster suppresses human glioma cell growth by targeting p27kip1. (PMID:19424584)
• Downregulation of miR-221 is associated with prostate tumor progression and recurrence. (PMID:19585579)
• Acute leukaemia evolving from myelodysplastic syndromes showed significantly decreased levels of miR-221 but not miR-222. (PMID:19615744)
• High miR-221 levels were associated with tumor multifocality of hepatocellular carcinoma and reduced time to recurrence after surgery. (PMID:19671867)
• Data show that Protein levels of tumor suppressor targets of the miRNAs were increased by antisense to miR-21 (PTEN and RECK) and miR-221 (p27). (PMID:19730150)
• Expression of miR-128b and miR-221 is down-regulated in MLL-rearranged ALL relative to other types of ALL. Reexpression of these miRNAs cooperatively sensitizes 2 cultured lines of MLL-AF4 ALL cells to glucocorticoids. (PMID:19749093)
• MiRNA-221 silencing rendered human bladder cancer T24 cells to undergo apoptosis induced by TRAIL. (PMID:19767219)
• The expression of p27(kip1) was up regulated in cells transfected with miR-221/ and miR-222 in glioblastoma cells. (PMID:19953484)
• results suggest that miR-221/222 overexpression might be one of the factors contributing to oncogenesis and progression of atypical teratoid-rhabdoid tumors through p27Kip1 downregulation (PMID:20012062)
• Data reveal an important contribution for miR-221 in hepatocarcinogenesis and suggest a role for DDIT4 dysregulation in this process. (PMID:20018759)
• miR-221 is involved in IFN-gamma-induced expression of ICAM-1 in cholangiocytes and further regulates inflammatory responses in cholangiopathies. (PMID:20110463)
• Data show that miR-221 is important in tumorigenesis of C, possibly by specifically down-regulating p27(Kip1), a cell-cycle inhibitor. (PMID:20146005)
• Suggest that miR-221/222 co-enhance the glioma malignant phenotype via activation of the Akt pathway mediated by regulation of common gene expression. (PMID:20198336)
• Increased expression of MIR221 is associated with chronic lymphocytic leukemia. (PMID:20203269)
• Studies indicate that human perinatal Hb switching is under control of the kit receptor/miR 221-222 complex. (PMID:20305142)
• data indicate several novel important associations for miRNAs in psoriasis and in particular the miR-221/2-TIMP3 target interaction could among others play a role in the psoriasis pathogenesis (PMID:20417062)
• These data indicate for the first time a mechanism involving STAT1/2 upregulation under the transcriptional control of INF-alpha signaling after knockdown of miR-221/222 cluster in U251 glioma cells. (PMID:20428775)
• MIR221 negatively regulates expression of CDKN1B (p27) and CDKN1C (p57)in ovarian surface epithelium and down-regulated in ovarian carcinomas. (PMID:20461750)
• Inhibition of PNPase by shRNA or stable overexpression of miR-221 protected melanoma cells from IFN-beta-mediated growth inhibition, accentuating the importance of PNPase induction and miR-221 down-regulation in mediating IFN-beta action. (PMID:20547861)
• The suppression of miR-221 plays a crucial role in the protection against apoptosis induced by ER stress in HCC cells. (PMID:20624000)
• Data indicate for the first time that miR-221/222 directly regulate apoptosis by targeting PUMA in glioblastoma and that miR-221/222 could be potential therapeutic targets for glioblastoma intervention. (PMID:20813046)
• The miR-221 is underactive towards p27-3’ UTR in quiescent cells, as a result of target site hindrance. (PMID:20818387)
• The direct amplification of plasma miR-221 can be used as a potential noninvasive molecular marker for diagnosis and prognosis of CRC (PMID:20880178)
• Low miR-221 expression is associated with recurrence of non-small cell lung cancer. (PMID:20975375)
• PUMA is a direct target of miR-221/222 that functions as an endogenous apoptosis regulator in these epithelial cancers. (PMID:21042732)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dre-mir-221	ENSDARG00000091272
mus_musculus	Mir221	ENSMUSG00000065422
rattus_norvegicus	Mir221	ENSRNOG00000035631

Paralogs (1): MIR222 (ENSG00000207725)

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.