ABSTRACT
In 1993 miRNAs were discovered during a research on Caenorhabditis elegans conducted by Victor Ambros and Gary Ruvkun. The gene lin-4 that played important role in development in C. elgans was observed not encoding any protein but a very small RNA molecule of just 22 nucleotides. Main objective of this review is to highlight the significance of miRNAs in regulating the expression of many genes, which are either directly or indirectly involved in many diseases. One of the major causes of illness and death in developed countries of the world is cardiovascular disease. Some of the miRNAs have certain role to play in heart that are not specified for heart. So miRNAs have been found to be in other tissues like fibroblasts, endothelial cells and smooth muscle cells that are part of physiological study of cardiovascular system. Adult heart has limited capacity of regeneration therefore lost cardiomyocytes due to myocardial ischemia or infarction can result in low performance of heart. miRNAs have been shown to play a role in apoptotic regulation of cardiomyocytes in vivo. Many studies have shown that miR146a and 155 are up regulated in peripheral blood mononuclear cells, synovial fibroblasts, synovial fluid and Th-17 cells from rheumatoid arthritis patients as compared to healthy persons. Several types of miRNAs are playing important roles in type 1 diabetes mellitus including miR-375 and miR-375 with intolerance to glucose and decreased beta cells account due to impaired proliferation. Up regulation of miR-125a in WAT of type 2 Diabetes mellitus have been observed. miRNAs have proved to be the important regulators of cytokines and growth factor expression. Thus, suggested as a good biomarker and target of therapy. miRNA profiling techniques have revealed the role of miRNAs in Multiple sclerosis
ABSTRACT
Background: Molecular marker based cancer diagnosis gaining more attention in the current genomics era. So, Hspb1 and Tp53 gene characterization and their mRNA expression might be helpful in diagnosis and prognosis of cat mammary adenocarcinoma. It will also add information in comparative cancer genetics and genomics
Objectives: Eight tumors of Siamese cats were analyzed to ascertain germ-line and tissue-specific somatic DNA variations of Hspb1 and Tp53 genes along with the ectopic differential expression in tumorous and normal tissues were also analyzed
Materials and Methods: Tumorous tissues and peripheral blood from mammary adenocarcinoma affected Siamese cats were collected from the Pet center-UVAS. DNA and RNA were extracted from these tissues to analyze the Hspb1 and Tp53 DNA variants and ectopic expression of their mRNA within cancerous and normal tissues
Results: Exon 1 and 3 revealed as hotspots in Hspb1 gene. The 5'UTR region of the exon1 bearsix mutation including 3 transitions, 2 transversion and one heterozygous synonymous transversion in two samples at locus c.34C>C/A. Exon 3 has 1 transversion at c.773A>A/T, 3'UTR of this exon harbor two point mutations at 1868A>T and 2193C>T loci. Intron 2 has two alterations at 1490C>C/T and GTCT4del at 1514. Overall up-regulation of Hspb1 gene was observed. While exons 3, 4 and 7 of Tp53 harbor a single variationat c.105A>A/G, c.465T>T/C and c.859G>T respectively. The locus c.1050G>G/A in exon 9 is a heterozygous [G/A] in 3 samples and homozygous [G] in 2 other tumours. Introns 3, 5, 7 and 9 harbor 3, 4, 2 and 7 altered loci respectively. Sixty percent of cancers showed up-regulated trend of Tp53 gene
Conclusions: Tumor specific mutations and ectopic expression of Hspb1 and Tp53 genes might be helpful in the diagnosis of the mammary lesions and endorse their involvement in cat mammary neoplasm