__NOTOC__ miR-214 is a vertebrate-specific family of

microRNA Micro ribonucleic acid (microRNA, miRNA, μRNA) are small, single-stranded, non-coding RNA molecules containing 21–23 nucleotides. Found in plants, animals, and even some viruses, miRNAs are involved in RNA silencing and post-transcr ...

precursors. The ~22

nucleotide Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...

mature miRNA sequence is excised from the precursor hairpin by the enzyme

Dicer Dicer, also known as endoribonuclease Dicer or helicase with RNase motif, is an enzyme that in humans is encoded by the gene. Being part of the RNase III family, Dicer cleaves double-stranded RNA (dsRNA) and pre-microRNA (pre-miRNA) into shor ...

. This sequence then associates with

RISC In electronics and computer science, a reduced instruction set computer (RISC) is a computer architecture designed to simplify the individual instructions given to the computer to accomplish tasks. Compared to the instructions given to a comp ...

which effects

RNA interference RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by ...

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 protein responsible for endocytosis in the eukaryotic cell. Dynamin is part of the "dynamin s ...

gene after the divergence of jawed and

jawless vertebrates Agnatha (; ) or jawless fish is a paraphyletic infraphylum of animals in the subphylum Vertebrata of the phylum Chordata, characterized by the lack of jaws. The group consists of both extant taxon, living (Cyclostomi, cyclostomes such as hagfish ...

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 Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

melanoma Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...

. Specifically, the mature microRNA excised from miR-214 is predicted to target two

activating protein 2 Activating Protein 2 (AP-2) is a family of closely related transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (geneti ...

transcription factors, bringing about downstream effects on a number of genes regulating vital

cell cycle The cell cycle, or cell-division cycle, is the sequential series of events that take place in a cell (biology), cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA (DNA re ...

processes, such as

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

, proliferation 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 mainly by processes of sprouting and ...

. miR-214 is also thought to regulate

type-I collagen Type I collagen is the most abundant collagen of the human body, consisting of around 90% of the body's total collagen in vertebrates. Due to this, it is also the most abundant protein type found in all vertebrates. Type I forms large, eosinoph ...

Role in cancer

miR-214 has been found to be downregulated in human

cervical cancer Cervical cancer is a cancer arising from the cervix or in any layer of the wall of the cervix. It is due to the abnormal growth of cells that can invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later sympt ...

; when miR-214 was upregulated in

HeLa HeLa () is an immortalized cell line used in scientific research. It is the oldest human cell line and one of the most commonly used. HeLa cells are durable and prolific, allowing for extensive applications in scientific study. The line is ...

cancer cells, it was found to significantly reduce cell growth. Two

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

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 int ...

. 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 ...

could bring about increased resistance to

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

. In human

glioma A glioma is a type of primary tumor that starts in the glial cells of the brain or spinal cord. They are malignant but some are extremely slow to develop. Gliomas comprise about 30% of all brain and central nervous system tumors and 80% of ...

cell line T98G expression of miR-214 has been shown to suppress expression of the

ubiquitin Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 19 ...

-conjugating enzyme 9 (UBC9) and reduces

tumour A neoplasm () is a type of abnormal and excessive growth of tissue (biology), tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tiss ...

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 w ...

, 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 myob ...

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