microRNA 21 also known as hsa-mir-21 or miRNA21 is a mammalian microRNA  that is encoded by the MIR21 gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

.

MIRN21 was one of the first mammalian microRNAs identified. The mature miR-21 sequence is strongly conserved throughout evolution. The human microRNA-21 gene is located on plus strand of chromosome 17q23.2 (55273409–55273480) within a coding gene TMEM49

TMEM49

Transmembrane protein 49 is a protein that in humans is encoded by the TMEM49 gene.-Further reading:...

 (also called vacuole membrane protein). Despite being located in intronic regions of a coding gene in the direction of transcription, it has its own promoter regions and forms a ~3433-nt long primary transcript of miR-21 (known as pri-miR-21) which is independently transcribed. The stem–loop recursor of miR-21(pre-miR-21) resides between nucleotides 2445 and 2516 of pri-miR-21.

Mature miR-21

Pri-miR-21 is cut by the endonuclease Drosha in the nucleus to produce pre-miR-21, which is exported into the cytosol

Cytosol

The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....

. This pre-miR-21 is then cut in to a short RNA duplex by Dicer

Dicer

Dicer is an endoribonuclease in the RNase III family that cleaves double-stranded RNA and pre-microRNA into short double-stranded RNA fragments called small interfering RNA about 20-25 nucleotides long, usually with a two-base overhang on the 3' end...

 in the cytosol. Although abundance of both strands is equal by transcription, only one strand (miR-21) is selected for processing as mature microRNA based on the thermodynamic stability of each end of the duplex, while the other strand (designated with an asterisk; miR-21*) is generally degraded. Mature microRNA is then loaded into microRNA ribonucleoprotein complex RISC (RNA-induced silencing complex

RNA-induced silencing complex

RNA-Induced Silencing Complex, or RISC, is a multiprotein complex that incorporates one strand of a small interfering RNA or micro RNA . RISC uses the siRNA or miRNA as a template for recognizing complementary mRNA. When it finds a complementary strand, it activates RNase and cleaves the RNA...

) and guided to target mRNAs with near perfect complimentarily at 3’UTR.

Targets

A number of targets for microRNA-21 have been experimentally validated and most of them are tumor suppressors

Tumor suppressor gene

A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...

. Notable targets include PTEN

PTEN

PTEN may mean:* Patterson-UTI Energy, Inc., which trades on the NASDAQ stock market under the symbol 'PTEN'* Prime Time Entertainment Network* PTEN , a human tumour suppressor gene on chromosome 10...

, PDCD4

PDCD4

Programmed cell death protein 4 is a protein that in humans is encoded by the PDCD4 gene. It is one of the targets of an oncomiR, MIRN21.-Interactions:PDCD4 has been shown to interact with RPS13 and Ribosomal protein L5.-Further reading:...

, Tropomyosin

Tropomyosin

Tropomyosin is an actin-binding protein that regulates actin mechanics. It is important, among other things, for muscle contraction. Tropomyosin, along with the troponin complex, associate with actin in muscle fibers and regulate muscle contraction by regulating the binding of myosin...

, Sprouty 1, Sprouty 2, Bcl2, RECK

RECK

Reversion-inducing-cysteine-rich protein with kazal motifs, also known as RECK, is a human gene, thought to be a metastasis suppressor.-Further reading:...

, IL-12p35

IL-12

IL-12 or IL 12 can refer to:Medicine* Interleukin 12Airplanes* Ilyushin Il-12Politics* Illinois' 12th congressional districtRoads* Illinois Route 12...

, JAG1

JAG1

JAG1 is a protein associated with Alagille syndrome. JAG1 has also been designated as CD339 .-External links:* *...

, HNRPK

HNRPK

Heterogeneous nuclear ribonucleoprotein K is a protein that in humans is encoded by the HNRNPK gene.-Interactions:HNRPK has been shown to interact with KHDRBS1, PCBP2, PTBP1, DDX1, PRMT1, HNRNPL and C-src tyrosine kinase.-Further reading:...

, BTG2

BTG2

Protein BTG2 also known as BTG family member 2 or NGF-inducible anti-proliferative protein PC3 or NGF-inducible protein TIS21, is a protein that in humans is encoded by the BTG2 gene and in other mammals by the homologous Btg2 gene...

, TGFBRII, TAp63, P12/CDK2AP1

CDK2AP1

Cyclin-dependent kinase 2-associated protein 1 is an enzyme that in humans is encoded by the CDK2AP1 gene.-Interactions:CDK2AP1 has been shown to interact with Cyclin-dependent kinase 2.-Further reading:...

, MEF2C

MEF2C

Myocyte-specific enhancer factor 2C also known as MADS box transcription enhancer factor 2, polypeptide C is a protein that in humans is encoded by the MEF2C gene. MEF2C is a transcription factor in the Mef2 family.-Genomics:...

, ANP32A, SMARCA4

SMARCA4

Transcription activator BRG1 also known as ATP-dependent helicase SMARCA4 is a protein that in humans is encoded by the SMARCA4 gene.- Function :...

, RhoB

RHOB

Ras homolog gene family, member B, also known as RHOB, is a protein which in humans is encoded by the RHOB gene.RHOB is a member of the Rho GTP-binding protein family.-Interactions:...

, and hMSH2

MSH2

MSH2 is a gene commonly associated with Hereditary nonpolyposis colorectal cancer.-Interactions:MSH2 has been shown to interact with Exonuclease 1, MSH3, MSH6, CHEK2, MAX, Ataxia telangiectasia and Rad3 related and BRCA1.-Further reading:...

.

Cancer

MiR-21 is one of the first microRNA to be described as an oncomir

Oncomir

An oncomir is a miRNA that is associated to cancer, for example, because it is found to be present in primary tumors or in tumor cell lines....

. As most of the targets of miR-21 are tumour suppressors, miR-21 is associated with a wide variety of cancers including that of breast

Breast cancer

Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

, ovaries

Ovarian cancer

Ovarian cancer is a cancerous growth arising from the ovary. Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses....

, cervix

Cervical cancer

Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. One of the most common symptoms is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer is in its advanced stages...

, colon, lung

Lung cancer

Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...

, liver

Liver cancer

Liver tumors or hepatic tumors are tumors or growths on or in the liver . Several distinct types of tumors can develop in the liver because the liver is made up of various cell types. These growths can be benign or malignant...

, brain

Brain tumor

A brain tumor is an intracranial solid neoplasm, a tumor within the brain or the central spinal canal.Brain tumors include all tumors inside the cranium or in the central spinal canal...

, oesophagus, prostate

Prostate cancer

Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...

, pancreas, and thyroid

Thyroid cancer

Thyroid neoplasm is a neoplasm or tumor of the thyroid. It can be a benign tumor such as thyroid adenoma, or it can be a malignant neoplasm , such as papillary, follicular, medullary or anaplastic thyroid cancer. Most patients are 25 to 65 years of age when first diagnosed; women are more affected...

.

Cardiac disease

miR-21 has been shown to play important role in development of heart disease. It is one of the microRNAs whose expression is increased in failing murine and human hearts. Further, inhibition of microRNAs in mice using chemically modified and cholesterol-conjugated miRNA inhibitors (antagomirs) was shown to inhibit interstitial fibrosis and improve cardiac function in a pressure- overload cardiac disease mice model. Surprisingly, miR-21 global knock-out mice did not show any overt phenotype when compared with wild type mice with respect to cardiac stress response. Similarly, short (8-nt) oligonucleotides designed to inhibit miR-21 could not inhibit cardiac hypertrophy or fibrosis. In another study with a mouse model of acute myocardial infarction, miR-21 expression was found to be significantly lower in infarcted areas and overexpression of miR-21 in those mice via adenovirus-mediated gene transfer decreased myocardial infarct size.

External links

• miRBase miR-21 family MIPF0000060