Microrna Essay

Another study conducted by researchers at Tel Aviv University—published in Nature Communications—hones in on the inverse correlation between the expression of oncosuppressor microRNA and a pre-established oncogene—a cancer development gene. The study says that this explains prolonged survival of pancreatic cancer, and the findings may very well yield future cultivation of effective drug cocktails for fighting not only multiple cancer types but also several other mortal diseases.

An abnormality in this process leads to a number of problems, including cancer. MicroRNAs are a type of RNA which inhibit the expression of genes and play a vital role in the development of cancer. Of notable interest is miR-378, as it increases tumor angiogenesis and growth and also enhances the survival of these cells, by decreasing the expression of tumor suppression genes like Sufu. A study testing human cell lines found that when Sufu expression levels were high, miR-378 expression levels were low, and when Sufu levels were low, miR-378 levels were high, showcasing that the two were negatively correlated. Because repression of Sufu can lead to rampant proliferation of cells, the inhibition of Sufu is essential in order for miR-378 to promote angiogenesis and increase cell

Structurally, miRNAs are initially transcribed from the genome as a long primary transcript that are cleaved or undergoes sequential processing by the RNAse III endonucleases Drosha and Dicer to yield the 17-23 mature nucleotide species (Kim, 2005). Mature miRNAs enters the RNA-induced silencing complex (RISC), thus a multiprotein complex that separate the mature strand from passenger strand and assists the interaction of mRNAs with miRNA that contain complementary sequences (Bader, 2012). As a result, mRNAs targeted by miRNA loads are either degraded or silenced in order not to be translated into protein. In the genome, a given miRNA can regulate several hundred transcripts whose molecules function within various cellular pathways including cell proliferation and apoptosis. To date, more than 50% of the activities of all protein-coding genes in mammals are controlled by miRNAs and greatly contributes to cell-type specific profiles of protein expression

siRNA shows the potential to selectively silence the expression of a disease gene based on the gene’s sequence. By down regulating cancerous transcripts and restoring the wild type function of a gene, siRNA has the potential to play an important role in cancer

MiR-21 has been found to be over expressed in 20 pancreatic carcinoma tissues and cell lines compared to normal tissue or cell lines. (15)

An increase in LIN28B expression can promote cancer progression due to the inhibition of let-7 miRNAs.

Cardiovascular disease (CVD) is the major macrovascular complication of diabetes mellitus as well as the main cause of death from clinical observation. There are about 75% of patients with type 2 diabetes have died of myocardial infarction as reported. Non-coding RNA (ncRNA) is an RNA molecule that is not translated into a protein, which include snoRNAs, microRNAs, siRNAs, piRNAs, lncRNAs and others. Recently, increasing number of evidences implicate that these ncRNAs are crucially involved in many cellular responses as well as physiological and pathological processes of several diseases. In this review, we summarize recent progress in research on functional regulatory of series of ncRNAs in cardiovascular disease with Diabetes Mellitus. Meanwhile,

This study aims to evaluate the prognostic effect of miRNA expression in stage II CRC patients. The research protocol follows the PRISMA-P (the Preferred Reporting

MicroRNAs are a class of small (17–25 nucleotides) single-stranded noncoding RNAs that function as a sequence-targeted modifiers of gene expression through translational repression [4]. The miRNAs are important key regulators of normal hematopoiesis and their disruption could lead to leukemogenesis [5]. Mutations like single-nucleotide polymorphisms located in microRNA binding sites can cause disruption in microRNA-target interactions, leading to deregulation of the target gene expression [6].

Saumet et al. in 2008 observed that miR-23a~27a~24-2 is directly repressed by the PML-RARA oncogene. also in some study upregulation of miR-23a has been observed in cancers(22). Considerable up-regulation of miR-23a was reported by Meng and Gottardo in human bladder cancer and in malignant cholangiocytes compared to normal tissues. Furthermore, Mi et al. in their study showed that miR-23a was among several other miRNAs that have been differentially expressed between acute myeloid leukemia (AMLs) and acute lymphoblastic leukemia (ALLs). In addition, up-regulation of miR-23a/b along with miR-24 has also been identified in osteoblast cell line (20,21).

A very promising approach for understanding the involvement of a certain miRNA in the process of a disease such as cancer, is to assess the miRNA expression profile of cancer patients, and to compare with their normal counterpart is a very promising approach for understanding the involvement of a certain miRNA in a disease of interest. This may lead to the discovery of a novel prognostic or diagnostic biomarker. Although, it is believed that miRNA profile from extracted total cellular RNA is an actual indicator of RISC complex-associated miRNA, due to quick degradation of non-guide miRNA, this hypothesis was challenged by the Cullen group, when they compared the miRNA profile of the total cellular miRNAs with the

Western blot showed that miR-138-5p could also inhibit the expression of PCNA, which was thought to be a proliferation biological marker13 .These results showed that miR-138-5p inhibited the proliferation of breast cancer cells.

Studies addressing in vivo modulation of miRNAs have previously used molecules consisting of modified nucleic acids, including 2-O-methyl modification, cholesterol conjugation, and locked nucleic acid oligomers. Early studies 45*, 46 demonstrate effective targeting of specific miRNAs in mammalian cells, but a significant issue is that target miRNAs are knocked down in other tissues 45*. Alternatively, the use of adenoassociated-virus (AAV) to either overexpress miRNAs via transgenes 22** or reduce miRNA expression via decoy miRNAs 47 have both been shown to be successful in vivo, and cardiac enriched AAV, such as AAV9 48*, may provide the advantage of tissue specific targeting. However, there are major challenges to be overcome prior to development of these as therapeutics, namely the currently limited understanding of effects caused by altered miRNA expression. Furthermore, understanding the implications of miRNA targeting outside the tissue of interest is imperative, as each tissue of the body appears to have its own dose/effect-relationship for individual miRNAs 49. Despite this, progress has been made in other fields, and highly specific antisense molecules have been successful in phase II clinical trials in the treatment of Duchene muscular dystrophy (DMD). DMD, however, is very different to AF, as focusing on a single miRNA can provide effective

In Archetype II lncRNA works to titrate proteins and protein factors away from chromatins, yet titrating them into nuclear subdomains while serving as decoys. This is common in miRNA sites where lncRNA appears as decoys. Acting as guides in Archetype III, lncRNA functions in either cis or trans regions to assist in the recruitment of chromatin enzymes for target genes. In cis, lncRNA occurs in co-transcriptionally. This suggests that lncRNAs acts as tethers. However, lncRNA are known to also act in trans when searching for target sites. This determines the importance chromosomal looping plays in cis effects (Rinn and Chang, 2012). During Archetype IV lncRNA forms ribonucleoproteins by acting as scaffolds (Kung, Colognori and Lee, 2013). Additionally, lncRNA in the regulation of gene expression was recent discovered in Xist, a regulatory transcript found in the X chromosome that mediates the silencing of gene expression (Malecová and Morris, 2010). According to Nagano and Fraser (2011), lncRNA is critical in genomic reprogramming. For instance, somatic cells that are reconditioned to induced pluripotent stem cells. LncRNA can also act as a post-transcriptional regulation in Mrna. A lncRNA known as Gomafu/MIAT hinders the formation of spliceosome and inhibits the splicing of one of the subsets involved in mRNA (Kung, Colognori and Lee, 2013).

MicroRNAs in cancer could act as oncogenes or tumor suppressor genes. They down-regulate tumor suppressor genes when functioning as oncogenes, on the contrary, by down-regulating oncogenes,