__NOTOC__ miR-214 is a vertebrate-specific family of microRNA precursors. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer. This sequence then associates with

RISC In computer engineering, a reduced instruction set computer (RISC) is a computer designed to simplify the individual instructions given to the computer to accomplish tasks. Compared to the instructions given to a complex instruction set comput ...

which effects RNA interference.

Origin and evolution of miR-214

miR-214 is a vertebrate-specific miR family that possesses one member in non-teleost vertebrates and two members in teleost fish. miR-214 is likely to have emerged within the

Dnm3 Dynamin-3 is a protein that in humans is encoded by the ''DNM3'' gene. The protein encoded by this gene is a member of the dynamin Dynamin is a GTPase responsible for endocytosis in the eukaryotic cell. Dynamin is part of the "dynamin superfam ...

gene after the divergence of jawed and

jawless vertebrates Agnatha (, Ancient Greek 'without jaws') is an infraphylum of jawless fish in the phylum Chordata, subphylum Vertebrata, consisting of both present (cyclostomes) and extinct ( conodonts and ostracoderms) species. Among recent animals, cyclosto ...

and is located on the opposite strand of an intron of Dnm3 and is associated in an expression cluster with miR-199.

Function

miR-214 is a "melano-miR", so-called because it is thought to encourage the metastasis of

melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...

. Specifically, the mature microRNA excised from miR-214 is predicted to target two activating protein 2 transcription factors, bringing about downstream effects on a number of genes regulating vital cell cycle processes, such as

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

proliferation Proliferation may refer to: Weapons *Nuclear proliferation, the spread of nuclear weapons, material, and technology *Chemical weapon proliferation, the spread of chemical weapons, material, and technology * Small arms proliferation, the spread of ...

and

angiogenesis Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting ...

. miR-214 is also thought to regulate type-I collagen.

Role in cancer

miR-214 has been found to be downregulated in human

cervical cancer Cervical cancer is a cancer arising from the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal ...

; when miR-214 was upregulated in HeLa cancer cells, it was found to significantly reduce cell growth. Two mRNA targets were identified as those encoding the proteins

MAP2K3 Dual specificity mitogen-activated protein kinase kinase 3 is an enzyme that in humans is encoded by the ''MAP2K3'' gene. The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This k ...

and

MAPK8 Mitogen-activated protein kinase 8 (also known as JNK1) is a ubiquitous enzyme that in humans is encoded by the ''MAPK8'' gene. Function The protein encoded by this gene is a member of the MAP kinase and JNK family. MAP kinases act as an integ ...

. The increased expression of miR-214 in

pancreatic cancer Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of t ...

could bring about increased resistance to chemotherapy. In human glioma cell line T98G expression of miR-214 has been shown to suppress expression of the ubiquitin-conjugating enzyme 9 (UBC9) and reduces tumour cell proliferation. The protein UBC9 is involved in the sumoylation pathway, and is up-regulated in many cancers.

Implication of miR-214 in skeletogenesis

miR-214, along with its cluster mate miR-199, has been shown to be implicated in skeleton formation. miR-214 has been shown to inhibit bone formation in human cell lines both by targeting

ATF4 Activating transcription factor 4 (tax-responsive enhancer element B67), also known as ATF4, is a protein that in humans is encoded by the ''ATF4'' gene. Function This gene encodes a transcription factor that was originally identified as a wi ...

, a gene encoding one of the maintranscription factors required for osteoblast function and by suppressing osteogenic differentiation of

C2C12 C2C12 is an immortalized mouse myoblast cell line. The C2C12 cell line is a subclone of myoblasts that were originally obtained by Yaffe and Saxel at the Weizmann Institute of Science in Israel in 1977. Developed for ''in vitro'' studies of myo ...

myoblast cells by targeting Sp7, an osteoblast-specific transcription factor. Also, Twist-1, which is a major actor in skeleton formation, regulates miR-199 and miR-214 cluster expression in mouse. Furthermore, miR199-214 cluster deletion in mouse lead to skeletal development abnormalities including craniofacial defects, neural arch and spinous processes malformations, and osteopenia. In zebrafish, miR-214 expression is mainly observed around developing skeletal elements.

References

{{miRNA precursor families MicroRNA