Aging is a significant risk factor for cancer which is due, in part, to heightened genomic instability. Mitotic surveillance proteins such as BubR1 play a pivotal role in ensuring accurate chromosomal segregation and preventing aneuploidy. BubR1 levels have been shown to naturally decline with age and its loss is associated with various age-related pathologies.
View Article and Find Full Text PDFG protein-coupled receptors (GPCRs) represent a large family of transmembrane proteins that transduce an external stimulus into a variety of cellular responses. They play a critical role in various pathological conditions in humans, including cancer, by regulating a number of key processes involved in tumor formation and progression. The epithelial-mesenchymal transition (EMT) is a fundamental process in promoting cancer cell invasion and tumor dissemination leading to metastasis, an often intractable state of the disease.
View Article and Find Full Text PDFNLRP3 pathway plays a vital role in the pathogenesis of different human cancers but still the regulation of NLRP3 pathway largely unknown. Therefore, we examined the levels of NLRP3 and its downstream components (caspase-1 and IL-1β) and its relationship with histone modifiers in renal cancer pathogenesis. Total 30 cases of clear cell renal cell carcinoma (ccRCC), were studied for NLRP3, caspase-1 and IL-1β expression using real-time PCR, which showed the augmented levels of all the three components of NLRP3 inflammasome pathway in ccRCC.
View Article and Find Full Text PDFObjective: Clear cell renal cell carcinoma (ccRCC) is one of the deadly diseases with poor metastatic disease prognosis. There is an urgent need to explore the potential molecular markers which can improve the prognosis of the disease. Histone demethylases have emerged as a powerful tool for cancer prognosis and therapeutics during the last decade.
View Article and Find Full Text PDFRenal cell carcinoma (RCC) is the leading cause among cancer-related deaths due to urological cancers, which results in response to combination of genetic and epigenetic factors. Histone methylations have been implicated in renal tumorigenesis but their clinical significance and underlying pathology are unexplored. Here, we elucidated the histone 3 lysine 4 (H3K4) methylation patterns in clear cell RCC and its underlying pathology.
View Article and Find Full Text PDFIndian J Clin Biochem
April 2019
Histone modifications occupy an essential position in the epigenetic landscape of the cell, and their alterations have been linked to cancers. Histone 3 lysine 4 (H3K4) methylation has emerged as a critical epigenetic cue for the regulation of gene transcription through dynamic modulation by several H3K4 methyltransferases (writers) and demethylases (erasers). Any disturbance in the delicate balance of writers and erasers can result in the mis-regulation of H3K4 methylation, which has been demonstrated in several human cancers.
View Article and Find Full Text PDFClinical heterogeneity is commonly observed in Wilson disease (WD), including cases with identical ATP7B mutations. It is thought to be an outcome of impairment in other genes involved in cellular copper homeostasis in addition to the mutations in the ATP7B gene. ATOX1, a copper chaperone that delivers copper to ATP7B, is a potential genetic modifier of WD.
View Article and Find Full Text PDFWilson disease (WD), a copper metabolism disorder, occurs due to the presence of mutations in the gene encoding ATP7B, a protein that primarily facilitates hepatic copper excretion. A better understanding of spectrum and functional significance of ATP7B variants is critical to formulating targeted and personalized therapies. Henceforth, we screened and sequenced 21 exons of ATP7B gene from 50 WD patients and 60 healthy subjects.
View Article and Find Full Text PDFRenal cell carcinoma is the most common form of the kidney cancer accounting for more than 85% of the cases of which clear cell renal cell carcinoma (ccRCC) is the major histological subtype. The central molecular signature for ccRCC pathogenesis is the biallelic inactivation of VHL gene due to the presence of mutations/hyper-methylation/complete gene loss, which results in the downstream HIF activation. These events lead to increased tyrosine kinase receptor signalling pathways (RAS/MEK/ERK pathway, PI3K/AKT/mTOR pathway and NF-κB pathway), which through their downstream effector proteins causes the cell to proliferate and migrate.
View Article and Find Full Text PDFThe regulation of histone 3 lysine 4 (H3K4) methylation code is indispensable for the cell as any disturbance in this has been associated with many pathologic conditions, like cancer. The SET domain-containing lysine methyltransferase 2 (KMT2) family of histone methyltransferases was the first to be identified as writers of H3K4 methylation. In mammals, seven members of the KMT2 family are responsible for carrying out the bulk of H3K4 methylation.
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