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Mir-26 MicroRNA Precursor Family
Origins The miR-26 microRNA is a small non-coding RNA that is involved in regulating gene expression. The miR-26 family is composed of miR-26a-1, miR-26a-2 and miR-26b located in chromosomes 3, 12 and 2, respectively. Pre-miR-26 with stem-loop structure is processed into mature miR-26 by a series of enzymes of intranuclear and intracytoplasm. The mature miRNA of miR-26a-1 and miR-26a-2 possesses the same sequence, with the exception of 2 different nucleotides in mature miR-26b. miR-26 appears to be a vertebrate specific microRNA and has now been predicted or experimentally validated in many vertebrate speciesMIPF0000043. Expressions miR-26 expression is induced in response to Hypoxia (medical), hypoxia and upregulated during smooth muscle cell (SMC) differentiation and neurogenesis. Moreover, miR-26 is consistently down-regulated in a wide range of malignant tumors, such as hepatocellular carcinoma, nasopharyngeal carcinoma, lung cancer, and breast cancer. On the contrary, miR-26a ...
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Secondary Structure
Protein secondary structure is the three dimensional form of ''local segments'' of proteins. The two most common secondary structural elements are alpha helices and beta sheets, though beta turns and omega loops occur as well. Secondary structure elements typically spontaneously form as an intermediate before the protein folds into its three dimensional tertiary structure. Secondary structure is formally defined by the pattern of hydrogen bonds between the amino hydrogen and carboxyl oxygen atoms in the peptide backbone. Secondary structure may alternatively be defined based on the regular pattern of backbone dihedral angles in a particular region of the Ramachandran plot regardless of whether it has the correct hydrogen bonds. The concept of secondary structure was first introduced by Kaj Ulrik Linderstrøm-Lang at Stanford in 1952. Other types of biopolymers such as nucleic acids also possess characteristic secondary structures. Types The most common secondary st ...
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Cholangiocarcinoma
Cholangiocarcinoma, also known as bile duct cancer, is a type of cancer that forms in the bile ducts. Symptoms of cholangiocarcinoma may include abdominal pain, yellowish skin, weight loss, generalized itching, and fever. Light colored stool or dark urine may also occur. Other biliary tract cancers include gallbladder cancer and cancer of the ampulla of Vater. Risk factors for cholangiocarcinoma include primary sclerosing cholangitis (an inflammatory disease of the bile ducts), ulcerative colitis, cirrhosis, hepatitis C, hepatitis B, infection with certain liver flukes, and some congenital liver malformations. However, most people have no identifiable risk factors. The diagnosis is suspected based on a combination of blood tests, medical imaging, endoscopy, and sometimes surgical exploration. The disease is confirmed by examination of cells from the tumor under a microscope. It is typically an adenocarcinoma (a cancer that forms glands or secretes mucin). Cholang ...
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C-myc
''Myc'' is a family of regulator genes and proto-oncogenes that code for transcription factors. The ''Myc'' family consists of three related human genes: ''c-myc'' ( MYC), ''l-myc'' ( MYCL), and ''n-myc'' ( MYCN). ''c-myc'' (also sometimes referred to as ''MYC'') was the first gene to be discovered in this family, due to homology with the viral gene ''v-myc''. In cancer, ''c-myc'' is often constitutively (persistently) expressed. This leads to the increased expression of many genes, some of which are involved in cell proliferation, contributing to the formation of cancer. A common human translocation involving ''c-myc'' is critical to the development of most cases of Burkitt lymphoma. Constitutive upregulation of ''Myc'' genes have also been observed in carcinoma of the cervix, colon, breast, lung and stomach. Myc is thus viewed as a promising target for anti-cancer drugs. Unfortunately, Myc possesses several features that render it undruggable such that any anti-cancer d ...
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In Vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and plants, as opposed to a tissue extract or dead organism. This is not to be confused with experiments done ''in vitro'' ("within the glass"), i.e., in a laboratory environment using test tubes, Petri dishes, etc. Examples of investigations ''in vivo'' include: the pathogenesis of disease by comparing the effects of bacterial infection with the effects of purified bacterial toxins; the development of non-antibiotics, antiviral drugs, and new drugs generally; and new surgical procedures. Consequently, animal testing and clinical trials are major elements of ''in vivo'' research. ''In vivo'' testing is often employed over ''in vitro'' because it is better suited for observing the overall effects of an experiment on a living subject. In dr ...
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Carcinogenesis
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnormal cell division. Cell division is a physiological process that occurs in almost all tissues and under a variety of circumstances. Normally, the balance between proliferation and programmed cell death, in the form of apoptosis, is maintained to ensure the integrity of tissues and organs. According to the prevailing accepted theory of carcinogenesis, the somatic mutation theory, mutations in DNA and epimutations that lead to cancer disrupt these orderly processes by interfering with the programming regulating the processes, upsetting the normal balance between proliferation and cell death. This results in uncontrolled cell division and the evolution of those cells by natural selection in the body. Only certain mutations lead to canc ...
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EZH2
Enhancer of zeste homolog 2 (EZH2) is a histone-lysine N-methyltransferase enzyme (EC 2.1.1.43) encoded by gene, that participates in histone methylation and, ultimately, transcriptional repression. EZH2 catalyzes the addition of methyl groups to histone H3 at lysine 27, by using the cofactor S-adenosyl-L-methionine. Methylation activity of EZH2 facilitates heterochromatin formation thereby silences gene function. Remodeling of chromosomal heterochromatin by EZH2 is also required during cell mitosis. EZH2 is the functional enzymatic component of the Polycomb Repressive Complex 2 (PRC2), which is responsible for healthy embryonic development through the epigenetic maintenance of genes responsible for regulating development and differentiation. EZH2 is responsible for the methylation activity of PRC2, and the complex also contains proteins required for optimal function ( EED, SUZ12, JARID2, AEBP2, RbAp46/48, and PCL). Mutation or over-expression of EZH2 has been linked ...
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Adeno-associated Virus
Adeno-associated viruses (AAV) are small viruses that infect humans and some other primate species. They belong to the genus '' Dependoparvovirus'', which in turn belongs to the family '' Parvoviridae''. They are small (approximately 26 nm in diameter) replication-defective, nonenveloped viruses and have linear single-stranded DNA (ssDNA) genome of approximately 4.8 kilobases (kb). AAV are not currently known to cause disease. The viruses cause a very mild immune response. Several additional features make AAV an attractive candidate for creating viral vectors for gene therapy, and for the creation of isogenic human disease models. Gene therapy vectors using AAV can infect both dividing and quiescent cells and persist in an extrachromosomal state without integrating into the genome of the host cell. In the native virus, however, integration of virally carried genes into the host genome does occur. Integration can be important for certain applications, but can also have unw ...
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Estrogen Receptor Alpha
Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein) that is activated by the sex hormone estrogen. In humans, ERα is encoded by the gene ''ESR1'' (EStrogen Receptor 1). Structure The estrogen receptor (ER) is a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription. Alternative splicing results in several ESR1 mRNA transcripts, which differ primarily in their 5-prime untranslated regions. The translated receptors show less variability. Ligands Agonists Non-selective * Endogenous estrogens (e.g., estradiol, estrone, estriol, estetrol) * Natural estrogens (e.g., conjugated equine estrogens) * Synthetic estrogens (e.g., ethinylestradiol, diethylstilbestrol) Selective Agonists of ERα selective over ERβ include: * Prop ...
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Cyclin E
Cyclin E is a member of the cyclin family. Cyclin E binds to G1 phase, G1 phase Cdk2, which is required for the transition from G1 to S phase of the cell cycle that determines initiation of DNA duplication. The Cyclin E/CDK2 complex phosphorylation, phosphorylates CDKN1B, p27Kip1 (an Enzyme inhibitor, inhibitor of Cyclin D), tagging it for degradation, thus promoting expression of Cyclin A, allowing progression to S phase. Functions of Cyclin E Like all cyclin family members, cyclin E forms a complex with cyclin-dependent kinase (CDK2). Cyclin E/CDK2 regulates multiple cellular processes by phosphorylating numerous downstream proteins. Cyclin E/CDK2 plays a critical role in the G1 phase and in the G1-S phase transition. Cyclin E/CDK2 phosphorylates retinoblastoma protein (Rb) to promote G1 progression. Hyper-phosphorylated Rb will no longer interact with E2F transcriptional factor, thus release it to promote expression of genes that drive cells to S phase through G1 phase. Cyc ...
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Cyclin D2
G1/S-specific cyclin-D2 is a protein that in humans is encoded by the ''CCND2'' gene. Function The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of cyclin-dependent kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/ S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. Knockout studies of the homologous gene in mouse suggest the essential roles of this gene in ovarian granulosa and germ cell proliferation. High level expression of this gene was observed in ovarian and testicular A testicle or testis (plur ...
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G1 Phase
The G1 phase, gap 1 phase, or growth 1 phase, is the first of four phases of the cell cycle that takes place in eukaryotic cell division. In this part of interphase, the cell synthesizes mRNA and proteins in preparation for subsequent steps leading to mitosis. G1 phase ends when the cell moves into the S phase of interphase. Around 30 to 40 percent of cell cycle time is spent in the G1 phase. Overview G1 phase together with the S phase and G2 phase comprise the long growth period of the cell cycle cell division called interphase that takes place before cell division in mitosis (M phase). During G1 phase, the cell grows in size and synthesizes mRNA and protein that are required for DNA synthesis. Once the required proteins and growth are complete, the cell enters the next phase of the cell cycle, S phase. The duration of each phase, including the G1 phase, is different in many different types of cells. In human somatic cells, the cell cycle lasts about 10 hours, and the G1 ...
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TGF-β
Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other signaling proteins. TGFB proteins are produced by all white blood cell lineages. Activated TGF-β complexes with other factors to form a serine/threonine kinase complex that binds to TGF-β receptors. TGF-β receptors are composed of both type 1 and type 2 receptor subunits. After the binding of TGF-β, the type 2 receptor kinase phosphorylates and activates the type 1 receptor kinase that activates a signaling cascade. This leads to the activation of different downstream substrates and regulatory proteins, inducing transcription of different target genes that function in differentiation, chemotaxis, proliferation, and activation of many immune cells. TGF-β is secreted by many cell types, including macrophages, in a latent form in whi ...
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