MIR222

Summary

MIR222 (microRNA 222, HGNC:31602) 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 407007 — 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:31602
Approved symbol	MIR222
Name	microRNA 222
Location	Xp11.3
Locus type	RNA, micro
Status	Approved
Aliases	hsa-mir-222
Ensembl gene	ENSG00000207725
Ensembl biotype	miRNA
OMIM	300569
Entrez	407007
RNAcentral	URS000075C381 — miRNA, 110 nt, 7 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 miRNA

ENST00000384992

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000384992 — 1 exons

Exon	Start	End
ENSE00001499999	45747015	45747124

Expression profiles

Bgee: expression breadth broad, 59 present calls, max score 76.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.4428 / max 705.5640, expressed in 1077 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199027	5.4428	1077

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	76.30	gold quality
placenta	UBERON:0001987	76.06	gold quality
monocyte	CL:0000576	74.59	gold quality
tibial artery	UBERON:0007610	73.49	gold quality
bone marrow	UBERON:0002371	73.32	gold quality
blood	UBERON:0000178	73.23	gold quality
adult mammalian kidney	UBERON:0000082	72.46	gold quality
gastrocnemius	UBERON:0001388	72.02	gold quality
body of uterus	UBERON:0009853	71.98	gold quality
esophagus mucosa	UBERON:0002469	70.80	gold quality
muscle layer of sigmoid colon	UBERON:0035805	70.23	gold quality
ascending aorta	UBERON:0001496	69.69	gold quality
lymph node	UBERON:0000029	69.35	gold quality
heart left ventricle	UBERON:0002084	69.24	gold quality
left coronary artery	UBERON:0001626	68.87	gold quality
omental fat pad	UBERON:0010414	68.55	gold quality
amygdala	UBERON:0001876	68.37	gold quality
gall bladder	UBERON:0002110	68.37	gold quality
liver	UBERON:0002107	68.07	silver quality
lower esophagus muscularis layer	UBERON:0035833	67.98	gold quality
body of stomach	UBERON:0001161	67.81	gold quality
transverse colon	UBERON:0001157	67.53	gold quality
anterior cingulate cortex	UBERON:0009835	67.17	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	67.13	gold quality
skin of abdomen	UBERON:0001416	67.03	gold quality
Brodmann (1909) area 9	UBERON:0013540	67.01	gold quality
hypothalamus	UBERON:0001898	66.92	gold quality
uterus	UBERON:0000995	66.76	gold quality
minor salivary gland	UBERON:0001830	66.69	gold quality
prostate gland	UBERON:0002367	66.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.95

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SNAI2

Literature-anchored findings (GeneRIF, showing 40)

• 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)
• MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1 (PMID:18708351)
• 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)
• Data suggest the involvement of miR-221 and miR-222 in the development or maintenance of the castration resistant prostate cancer phenotype. (PMID:19351832)
• Results suggested that hsa-miR-222 regulates the MMP1 expression through both direct cis-regulatory mechanism (targeting MMP1 mRNA) and indirect trans-regulatory mechanism (indirect controlling of MMP1 gene expression by targeting SOD2). (PMID:19487542)
• Results show that Dicer is responsible for the generation of the mature miR-222 and -339, which suppress ICAM-1 expression on tumor cells. (PMID:19520829)
• study provides the first evidence for an oncogenic activity of miR-155, miR-203, miR-210 and miR-222 in the development of pancreatic cancer as has been reported for other tumor types (PMID:19551852)
• participates in endometrial stromal cell differentiation by regulating ESCs terminally withdrawing from the cell cycle (PMID:19589872)
• Acute leukaemia evolving from myelodysplastic syndromes showed significantly decreased levels of miR-221 but not miR-222. (PMID:19615744)
• Data show that miR-15a in BM and miR-16 in PB were differentially expressed between low-risk and high-risk groups, while miR-222 and miR-181a expression was higher in AML than in MDS in both BM and PB. (PMID:19883312)
• 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)
• Our study showed that miR-222 overexpression is common in HCC and could confer metastatic potentials in HCC cells, possibly through activating AKT signaling. (PMID:20103675)
• 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 MIR222 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)
• MIR222 negatively regulates expression of CDKN1B (p27) and CDKN1C (p57) in ovarian surface epithelium and down-regulated in ovarian carcinomas. (PMID:20461750)
• miR-222 acts as an antiangiogenic miRNA, by controlling STAT5A expression. (PMID:20489169)
• Our findings suggest a direct role of miR-222 and miR-21 in conferring resistance to fludarabine chemotherapy in chronic lymphocytic leukemia (PMID:20504344)
• The suppression of miR-222 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 PUM1 binding induces a local change in RNA structure that favours association with miR-222, efficient suppression of p27 expression, and rapid entry to the cell cycle. (PMID:20818387)
• Up-regulation of miRNA222 is associated with bladder carcinoma. (PMID:20857258)
• PUMA is a direct target of miR-221/222 that functions as an endogenous apoptosis regulator in these epithelial cancers. (PMID:21042732)
• study investigated role of miR-221/222 in hormone-independent growth and acquired resistance to fulvestrant of breast cancer cells (PMID:21057537)
• High microRNA 222 is associated with prostate cancer. (PMID:21071579)
• Data suggest that CBFL-associated fusion proteins may lead to up-regulation of the KIT receptor by down-regulating MIR-222/221. (PMID:21076613)
• Down-regulation of miR-222 correlates with pronounced Kit expression and is associated with gastrointestinal stromal tumors. (PMID:21132270)
• Overexpression of miR-222 was associated with recurrence and distant metastases in thyroid carcinoma. (PMID:21537871)
• miR-221/222 were downregulated by endoplasmic reticulum stress in human hepatocellular carcinoma cells, which protected cells from apoptosis. (PMID:21586237)
• These results suggested that HMGA1 is a positive regulator of miR-222, and HMGA1 overexpression might contribute to dysregulation of Akt signaling in NSCLC (PMID:21656127)
• TRPS1 targeting by miR-221/222 promotes the epithelial-to-mesenchymal transition in breast cancer (PMID:21673316)
• Data show that showed that miR-130a, expressed at low level in lung cancer cell lines, by targeting MET was able to reduce TRAIL resistance in non-small cell lung cancer (NSCLC) cells through the c-Jun-mediated downregulation of miR-221 and miR-222. (PMID:21706050)
• The proto-oncogene ETS-1, involved in the pathogenesis of cancers of different origin, is a transcriptional regulator of miR-222 by direct binding to its promoter region. (PMID:21711453)
• Results suggest that miR-221 and -222 regulate glioma tumorigenesis at least in part through the control of PTPmu protein expression. (PMID:21743492)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dre-mir-222a	ENSDARG00000090347
mus_musculus	Mir222	ENSMUSG00000065471
rattus_norvegicus	Mir222	ENSRNOG00000035581

Paralogs (1): MIR221 (ENSG00000207870)

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.