Mir221 (microRNA 221) - Rat Genome Database

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Gene: Mir221 (microRNA 221) Rattus norvegicus
Symbol: Mir221
Name: microRNA 221
RGD ID: 2325451
Description: Predicted to enable mRNA base-pairing translational repressor activity. Involved in several processes, including negative regulation of osteoblast differentiation; positive regulation of Schwann cell migration; and positive regulation of Schwann cell proliferation. Predicted to be located in synapse. Predicted to be part of RISC complex. Biomarker of breast cancer; diabetes mellitus; hepatocellular carcinoma; and sciatic neuropathy. Human ortholog(s) of this gene implicated in gastrointestinal stromal tumor; hepatocellular carcinoma; and oral squamous cell carcinoma. Orthologous to human MIR221 (microRNA 221); INTERACTS WITH 2-acetamidofluorene; aflatoxin B1; atrazine.
Type: ncrna (Ensembl: miRNA)
Previously known as: microRNA mir-221; rno-mir-221
RGD Orthologs
Alliance Genes
More Info more info ...
Latest Assembly: mRatBN7.2 - mRatBN7.2 Assembly
Rat AssemblyChrPosition (strand)SourceGenome Browsers
mRatBN7.2X3,429,465 - 3,429,573 (+)NCBImRatBN7.2mRatBN7.2
mRatBN7.2 EnsemblX3,429,465 - 3,429,573 (+)EnsemblmRatBN7.2 Ensembl
UTH_Rnor_SHR_UtxX3,495,164 - 3,495,272 (+)NCBIRnor_SHRUTH_Rnor_SHR_Utx
UTH_Rnor_SHRSP_BbbUtx_1.0X6,970,960 - 6,971,068 (+)NCBIRnor_SHRSPUTH_Rnor_SHRSP_BbbUtx_1.0
UTH_Rnor_WKY_Bbb_1.0X3,288,051 - 3,288,159 (+)NCBIRnor_WKYUTH_Rnor_WKY_Bbb_1.0
Rnor_6.0X3,684,480 - 3,684,588 (+)NCBIRnor6.0Rnor_6.0rn6Rnor6.0
Rnor_6.0 EnsemblX3,684,480 - 3,684,588 (+)EnsemblRnor6.0rn6Rnor6.0
Rnor_5.0X4,475,295 - 4,475,403 (+)NCBIRnor5.0Rnor_5.0rn5Rnor5.0
CeleraX3,969,242 - 3,969,350 (+)NCBICelera
Cytogenetic MapXq11NCBI
JBrowse: View Region in Genome Browser (JBrowse)

Gene Ontology Annotations     Click to see Annotation Detail View

Biological Process
cellular response to amino acid stimulus  (ISO)
cellular response to decreased oxygen levels  (ISO)
cellular response to forskolin  (ISO)
cellular response to glucose stimulus  (IEP)
cellular response to inorganic substance  (ISO)
cellular response to nerve growth factor stimulus  (IEP)
cellular response to tumor necrosis factor  (ISO)
inflammatory response  (ISO)
long-term synaptic potentiation  (ISO)
miRNA-mediated gene silencing by inhibition of translation  (ISO)
miRNA-mediated post-transcriptional gene silencing  (ISO)
negative regulation of apoptotic process  (ISO)
negative regulation of cell adhesion molecule production  (ISO)
negative regulation of cell migration involved in sprouting angiogenesis  (ISO)
negative regulation of cell population proliferation  (ISO)
negative regulation of double-strand break repair  (ISO)
negative regulation of ERK1 and ERK2 cascade  (ISO)
negative regulation of hematopoietic stem cell proliferation  (ISO)
negative regulation of heterotypic cell-cell adhesion  (ISO)
negative regulation of inflammatory response  (ISO)
negative regulation of interleukin-21 production  (ISO)
negative regulation of leukocyte adhesion to vascular endothelial cell  (ISO)
negative regulation of necroptotic process  (ISO)
negative regulation of osteoblast differentiation  (IMP)
negative regulation of sprouting angiogenesis  (ISO)
negative regulation of TRAIL-activated apoptotic signaling pathway  (ISO)
negative regulation of vascular associated smooth muscle cell differentiation  (ISO)
platelet-derived growth factor receptor signaling pathway  (ISO)
positive regulation of apoptotic process  (ISO)
positive regulation of blood vessel endothelial cell migration  (ISO)
positive regulation of epithelial cell migration  (ISO)
positive regulation of epithelial to mesenchymal transition  (ISO)
positive regulation of erythrocyte differentiation  (ISO)
positive regulation of G1/S transition of mitotic cell cycle  (ISO)
positive regulation of receptor signaling pathway via JAK-STAT  (ISO)
positive regulation of Schwann cell migration  (IMP)
positive regulation of Schwann cell proliferation  (IMP)
positive regulation of tyrosine phosphorylation of STAT protein  (ISO)
positive regulation of vascular associated smooth muscle cell dedifferentiation  (ISO)
positive regulation of vascular associated smooth muscle cell migration  (ISO)
positive regulation of vascular associated smooth muscle cell proliferation  (ISO)
positive regulation of wound healing, spreading of epidermal cells  (ISO)
response to estradiol  (IEP)
response to glucose  (ISO)
response to oxygen levels  (ISO)
sensory perception of sound  (ISO)
Wnt signaling pathway  (ISO)

Cellular Component
RISC complex  (ISO)
synapse  (ISO)

Molecular Function


References - curated
# Reference Title Reference Citation
1. MicroRNA-221 governs tumor suppressor HDAC6 to potentiate malignant progression of liver cancer. Bae HJ, etal., J Hepatol. 2015 Aug;63(2):408-19. doi: 10.1016/j.jhep.2015.03.019. Epub 2015 Mar 25.
2. Circulating Plasma Levels of MicroRNA-21 and MicroRNA-221 Are Potential Diagnostic Markers for Primary Intrahepatic Cholangiocarcinoma. Correa-Gallego C, etal., PLoS One. 2016 Sep 29;11(9):e0163699. doi: 10.1371/journal.pone.0163699. eCollection 2016.
3. Evaluation of circulating miR-21 and miR-222 as diagnostic biomarkers for gastric cancer. Emami SS, etal., J Cancer Res Ther. 2019 Jan-Mar;15(1):115-119. doi: 10.4103/jcrt.JCRT_592_17.
4. In Hepatocellular Carcinoma miR-221 Modulates Sorafenib Resistance through Inhibition of Caspase-3-Mediated Apoptosis. Fornari F, etal., Clin Cancer Res. 2017 Jul 15;23(14):3953-3965. doi: 10.1158/1078-0432.CCR-16-1464. Epub 2017 Jan 17.
5. miR-221-3p and miR-222-3p downregulation promoted osteogenic differentiation of bone marrow mesenchyme stem cells through IGF-1/ERK pathway under high glucose condition. Gan K, etal., Diabetes Res Clin Pract. 2020 Sep;167:108121. doi: 10.1016/j.diabres.2020.108121. Epub 2020 Mar 16.
6. Targeting hepatic miR-221/222 for therapeutic intervention of nonalcoholic steatohepatitis in mice. Jiang X, etal., EBioMedicine. 2018 Nov;37:307-321. doi: 10.1016/j.ebiom.2018.09.051. Epub 2018 Oct 10.
7. Correlation of the Levels of microRNA with Cell Composition of Axillary Lymph Node in Wistar Rats with Breast Cancer. Kabakov AV, etal., Bull Exp Biol Med. 2020 Feb;168(4):500-502. doi: 10.1007/s10517-020-04740-w. Epub 2020 Mar 10.
8. Down-regulation of miR-221 and miR-222 correlates with pronounced Kit expression in gastrointestinal stromal tumors. Koelz M, etal., Int J Oncol. 2011 Feb;38(2):503-11. doi: 10.3892/ijo.2010.857. Epub 2010 Dec 3.
9. miR-221 suppression through nanoparticle-based miRNA delivery system for hepatocellular carcinoma therapy and its diagnosis as a potential biomarker. Li F, etal., Int J Nanomedicine. 2018 Apr 13;13:2295-2307. doi: 10.2147/IJN.S157805. eCollection 2018.
10. Oroxin B Induces Apoptosis by Down-Regulating MicroRNA-221 Resulting in the Inactivation of the PTEN/PI3K/AKT Pathway in Liver Cancer. Li N, etal., Molecules. 2019 Nov 30;24(23). pii: molecules24234384. doi: 10.3390/molecules24234384.
11. A microRNA 221- and 222-mediated feedback loop maintains constitutive activation of NFκB and STAT3 in colorectal cancer cells. Liu S, etal., Gastroenterology. 2014 Oct;147(4):847-859.e11. doi: 10.1053/j.gastro.2014.06.006. Epub 2014 Jun 12.
12. MicroRNA-221-3p promotes pulmonary artery smooth muscle cells proliferation by targeting AXIN2 during pulmonary arterial hypertension. Nie X, etal., Vascul Pharmacol. 2019 May;116:24-35. doi: 10.1016/j.vph.2017.07.002. Epub 2017 Jul 8.
13. MicroRNA-221/222 upregulation indicates the activation of stellate cells and the progression of liver fibrosis. Ogawa T, etal., Gut. 2012 Nov;61(11):1600-9. doi: 10.1136/gutjnl-2011-300717. Epub 2012 Jan 20.
14. MicroRNA deregulation in human thyroid papillary carcinomas. Pallante P, etal., Endocr Relat Cancer. 2006 Jun;13(2):497-508. doi: 10.1677/erc.1.01209.
15. Estradiol-mediated regulation of hepatic iNOS in obese rats: Impact of Src, ERK1/2, AMPKα, and miR-221. Panic A, etal., Biotechnol Appl Biochem. 2018 Nov;65(6):797-806. doi: 10.1002/bab.1680. Epub 2018 Aug 6.
16. miR-221 silencing blocks hepatocellular carcinoma and promotes survival. Park JK, etal., Cancer Res. 2011 Dec 15;71(24):7608-16. doi: 10.1158/0008-5472.CAN-11-1144. Epub 2011 Oct 18.
17. ClinVar Automated Import and Annotation Pipeline RGD automated import pipeline for ClinVar variants, variant-to-disease annotations and gene-to-disease annotations
18. Data Import for Chemical-Gene Interactions RGD automated import pipeline for gene-chemical interactions
19. MicroRNA-221 regulates FAS-induced fulminant liver failure. Sharma AD, etal., Hepatology. 2011 May;53(5):1651-61. doi: 10.1002/hep.24243. Epub 2011 Mar 11.
20. MicroRNA-31 activates the RAS pathway and functions as an oncogenic MicroRNA in human colorectal cancer by repressing RAS p21 GTPase activating protein 1 (RASA1). Sun D, etal., J Biol Chem. 2013 Mar 29;288(13):9508-18. doi: 10.1074/jbc.M112.367763. Epub 2013 Jan 15.
21. Sustained activation of ERK1/2 by NGF induces microRNA-221 and 222 in PC12 cells. Terasawa K, etal., FEBS J. 2009 Jun;276(12):3269-76. doi: 10.1111/j.1742-4658.2009.07041.x. Epub 2009 Apr 25.
22. MicroRNA-221/222 Family Counteracts Myocardial Fibrosis in Pressure Overload-Induced Heart Failure. Verjans R, etal., Hypertension. 2018 Feb;71(2):280-288. doi: 10.1161/HYPERTENSIONAHA.117.10094. Epub 2017 Dec 18.
23. Inhibition of MicroRNA-221 Alleviates Neuropathic Pain Through Targeting Suppressor of Cytokine Signaling 1. Xia L, etal., J Mol Neurosci. 2016 Jul;59(3):411-20. doi: 10.1007/s12031-016-0748-1. Epub 2016 Apr 8.
24. miR-221 and miR-222 expression increased the growth and tumorigenesis of oral carcinoma cells. Yang CJ, etal., J Oral Pathol Med. 2011 Aug;40(7):560-6. doi: 10.1111/j.1600-0714.2010.01005.x. Epub 2011 Jan 13.
25. miR-221 and miR-222 promote Schwann cell proliferation and migration by targeting LASS2 after sciatic nerve injury. Yu B, etal., J Cell Sci. 2012 Jun 1;125(Pt 11):2675-83. doi: 10.1242/jcs.098996. Epub 2012 Mar 5.
Additional References at PubMed
PMID:14691248   PMID:16381832   PMID:16682203   PMID:17604727   PMID:17805466   PMID:18723672   PMID:19147652   PMID:19150885   PMID:19188425   PMID:20403161   PMID:20548288   PMID:21993888  
PMID:23185045   PMID:23390134   PMID:23646144   PMID:24015301   PMID:24604335   PMID:25135725   PMID:25858512   PMID:26232787   PMID:27113449   PMID:27412651   PMID:28821887   PMID:29577996  
PMID:29693157   PMID:30463111   PMID:31587871   PMID:31878844   PMID:32305038   PMID:32648125   PMID:32858649   PMID:33313941   PMID:34018345   PMID:34519137   PMID:34687039   PMID:35186224  
PMID:35591810   PMID:36690096   PMID:37270133  


Comparative Map Data
(Rattus norvegicus - Norway rat)
Rat AssemblyChrPosition (strand)SourceGenome Browsers
mRatBN7.2X3,429,465 - 3,429,573 (+)NCBImRatBN7.2mRatBN7.2
mRatBN7.2 EnsemblX3,429,465 - 3,429,573 (+)EnsemblmRatBN7.2 Ensembl
UTH_Rnor_SHR_UtxX3,495,164 - 3,495,272 (+)NCBIRnor_SHRUTH_Rnor_SHR_Utx
UTH_Rnor_SHRSP_BbbUtx_1.0X6,970,960 - 6,971,068 (+)NCBIRnor_SHRSPUTH_Rnor_SHRSP_BbbUtx_1.0
UTH_Rnor_WKY_Bbb_1.0X3,288,051 - 3,288,159 (+)NCBIRnor_WKYUTH_Rnor_WKY_Bbb_1.0
Rnor_6.0X3,684,480 - 3,684,588 (+)NCBIRnor6.0Rnor_6.0rn6Rnor6.0
Rnor_6.0 EnsemblX3,684,480 - 3,684,588 (+)EnsemblRnor6.0rn6Rnor6.0
Rnor_5.0X4,475,295 - 4,475,403 (+)NCBIRnor5.0Rnor_5.0rn5Rnor5.0
CeleraX3,969,242 - 3,969,350 (+)NCBICelera
Cytogenetic MapXq11NCBI
(Homo sapiens - human)
Human AssemblyChrPosition (strand)SourceGenome Browsers
GRCh38X45,746,157 - 45,746,266 (-)NCBIGRCh38GRCh38hg38GRCh38
GRCh38.p14 EnsemblX45,746,157 - 45,746,266 (-)EnsemblGRCh38hg38GRCh38
GRCh37X45,605,585 - 45,605,694 (-)NCBIGRCh37GRCh37hg19GRCh37
Build 36X45,490,528 - 45,490,637 (-)NCBINCBI36Build 36hg18NCBI36
CeleraX49,797,482 - 49,797,591 (-)NCBICelera
Cytogenetic MapXp11.3NCBI
HuRefX43,320,976 - 43,321,084 (-)NCBIHuRef
CHM1_1X45,638,042 - 45,638,151 (-)NCBICHM1_1
T2T-CHM13v2.0X45,155,612 - 45,155,721 (-)NCBIT2T-CHM13v2.0
(Mus musculus - house mouse)
Mouse AssemblyChrPosition (strand)SourceGenome Browsers
GRCm39X19,012,533 - 19,012,627 (-)NCBIGRCm39GRCm39mm39
GRCm39 EnsemblX19,012,533 - 19,012,627 (-)EnsemblGRCm39 Ensembl
GRCm38X19,146,294 - 19,146,388 (-)NCBIGRCm38GRCm38mm10GRCm38
GRCm38.p6 EnsemblX19,146,294 - 19,146,388 (-)EnsemblGRCm38mm10GRCm38
MGSCv37X18,723,420 - 18,723,514 (-)NCBIGRCm37MGSCv37mm9NCBIm37
CeleraX16,722,452 - 16,722,546 (-)NCBICelera
Cytogenetic MapXA1.3NCBI
cM MapX14.52NCBI
(Canis lupus familiaris - dog)
Dog AssemblyChrPosition (strand)SourceGenome Browsers
CanFam3.1X39,523,890 - 39,523,951 (-)NCBICanFam3.1CanFam3.1canFam3CanFam3.1
CanFam3.1 EnsemblX39,523,885 - 39,523,954 (-)EnsemblCanFam3.1canFam3CanFam3.1
Dog10K_Boxer_TashaX26,756,912 - 26,756,973 (-)NCBIDog10K_Boxer_Tasha
ROS_Cfam_1.0X39,655,841 - 39,655,902 (-)NCBIROS_Cfam_1.0
UMICH_Zoey_3.1X39,646,201 - 39,646,262 (-)NCBIUMICH_Zoey_3.1
UNSW_CanFamBas_1.0X39,633,218 - 39,633,279 (-)NCBIUNSW_CanFamBas_1.0
UU_Cfam_GSD_1.0X39,725,537 - 39,725,598 (-)NCBIUU_Cfam_GSD_1.0
(Sus scrofa - pig)
Pig AssemblyChrPosition (strand)SourceGenome Browsers
Sscrofa11.1 EnsemblX40,571,068 - 40,571,137 (-)EnsemblSscrofa11.1susScr11Sscrofa11.1
Sscrofa11.1X40,571,068 - 40,571,137 (-)NCBISscrofa11.1Sscrofa11.1susScr11Sscrofa11.1
Sscrofa10.2X45,274,873 - 45,274,942 (-)NCBISscrofa10.2Sscrofa10.2susScr3

miRNA Target Status

Confirmed Targets
Gene TargetMature miRNAMethod NameResult TypeData TypeSupport TypePMID
Cdkn1brno-miR-221-3pMirtarbaseexternal_infoqRT-PCR//Luciferase reporter assay//Western blotFunctional MTI19150885
Bcl2l11rno-miR-221-3pMirtarbaseexternal_infoImmunoblot//Luciferase reporter assay//qRT-PCR//ReFunctional MTI19438724

Predicted Targets
Summary Value
Count of predictions:8631
Count of gene targets:5787
Count of transcripts:6320
Interacting mature miRNAs:rno-miR-221-3p, rno-miR-221-5p
Prediction methods:Microtar, Miranda, Pita, Rnahybrid, Targetscan
Result types:miRGate_prediction

The detailed report is available here: Full Report CSV TAB Printer

miRNA Target Status data imported from miRGate (http://mirgate.bioinfo.cnio.es/).
For more information about miRGate, see PMID:25858286 or access the full paper here.

QTLs in Region (mRatBN7.2)
The following QTLs overlap with this region.    Full Report CSV TAB Printer Gviewer
RGD IDSymbolNameLODP ValueTraitSub TraitChrStartStopSpecies
731181Uae27Urinary albumin excretion QTL 272.70.0059urine albumin amount (VT:0002871)urine albumin excretion rate (CMO:0000757)X143491017Rat
70166Bp65Blood pressure QTL 655.8arterial blood pressure trait (VT:2000000)systolic blood pressure (CMO:0000004)X144797211374346Rat
634325Bw13Body weight QTL 130body mass (VT:0001259)body weight (CMO:0000012)X144797220991088Rat
70165Bp64Blood pressure QTL 645.2arterial blood pressure trait (VT:2000000)systolic blood pressure (CMO:0000004)X144812931706553Rat
631204Gluco15Glucose level QTL 150.001blood glucose amount (VT:0000188)blood glucose level area under curve (AUC) (CMO:0000350)X162371522646544Rat
1298071Edpm12Estrogen-dependent pituitary mass QTL 123.2pituitary gland mass (VT:0010496)pituitary gland wet weight (CMO:0000853)X292789847927898Rat


RNA-SEQ Expression
High: > 1000 TPM value   Medium: Between 11 and 1000 TPM
Low: Between 0.5 and 10 TPM   Below Cutoff: < 0.5 TPM

alimentary part of gastrointestinal system circulatory system endocrine system exocrine system hemolymphoid system hepatobiliary system integumental system musculoskeletal system nervous system renal system reproductive system respiratory system appendage
Medium 3 1
Low 1 9 21 5 17 5 5 5 27 11 19 9 5
Below cutoff 2 7 2 2 2 1 4 9 5


Nucleotide Sequences
RefSeq Transcripts NR_031934 (Get FASTA)   NCBI Sequence Viewer   Search GEO for Microarray Profiles
GenBank Nucleotide JACYVU010000342 (Get FASTA)   NCBI Sequence Viewer   Search GEO for Microarray Profiles

RefSeq Acc Id: ENSRNOT00000053754
Rat AssemblyChrPosition (strand)Source
mRatBN7.2 EnsemblX3,429,465 - 3,429,573 (+)Ensembl
Rnor_6.0 EnsemblX3,684,480 - 3,684,588 (+)Ensembl
RefSeq Acc Id: NR_031934
Rat AssemblyChrPosition (strand)Source
mRatBN7.2X3,429,465 - 3,429,573 (+)NCBI
Rnor_6.0X3,684,480 - 3,684,588 (+)NCBI
Rnor_5.0X4,475,295 - 4,475,403 (+)NCBI
CeleraX3,969,242 - 3,969,350 (+)NCBI

eQTL   View at Phenogen
WGCNA   View at Phenogen
Tissue/Strain Expression   View at Phenogen

Additional Information

Database Acc Id Source(s)
AGR Gene RGD:2325451 AgrOrtholog
BioCyc Gene G2FUF-3140 BioCyc
Ensembl Genes ENSRNOG00000035631 Ensembl, ENTREZGENE
Ensembl Transcript ENSRNOT00000053754 ENTREZGENE
miRBase MI0000961 ENTREZGENE
NCBI Gene 100314163 ENTREZGENE
PhenoGen Mir221 PhenoGen
RatGTEx ENSRNOG00000035631 RatGTEx
RNAcentral URS0000170CF4 RNACentral
  URS000075AF41 RNACentral
  URS000075CB96 RNACentral

Nomenclature History
Date Current Symbol Current Name Previous Symbol Previous Name Description Reference Status
2013-08-14 Mir221  microRNA 221  Mir221  microRNA mir-221  Nomenclature updated to reflect human and mouse nomenclature 1299863 APPROVED
2010-06-02 Mir221  microRNA mir-221      Symbol and Name status set to provisional 70820 PROVISIONAL