Metabolic reprogramming, such as enhanced aerobic glycolysis, allows cancer cells to maintain viability and promote proliferation. It is one of the major consequences of oncogenic mutations. KRAS is the most frequently mutated oncogene in human cancer. It is thought to be closely related to metabolic reprogramming. However, it is not clear whether it can participate in metabolic reprogramming by directly regulating metabolic enzymes. Additionally, the functional differences among the splice variants of KRAS have not been determined. In a study, recently published in Nature, Amendola et al reported a unique interaction between one of the KRAS splice variants (KRAS4A) and the major glycolytic enzyme (hexokinase 1) in cancer cells. Their findings indicated that a better understanding on the regulation of hexokinase 1 by KRAS may reveal novel therapeutic strategies.
Cancer can be identified as an uncontrolled growth and reproduction of cell. Accumulation of genetic aberrations (mutations of oncogenes and tumor-suppressor genes and epigenetic modifications) is one of the characteristics of cancer cell. Increasing number of studies highlighted importance of the epigenetic alterations in cancer treatment and prognosis. Now, cancer epigenetics have a huge importance for developing novel biomarkers and therapeutic target for cancer. In this review, we will provide a summary of the major epigenetic changes involved in cancer and preclinical results of epigenetic therapeutics.
Polymorphisms in the C-reactive protein (CRP) genes might have crucial role in the development of metabolic syndrome (MetS). In the current comprehensive meta-analyses, we aim to provide a quantitative assessment of the association between CRP single-nucleotide polymorphisms (SNPs) and the risk of MetS. An electronic search was performed on several databases. After data extraction, random effect model was used to calculate the pooled odds ratio (OR) and 95% confidence intervals (CIs). Four independent studies including case-control, cohort, and cross-sectional methods were analyzed. Our meta-analysis indicated that CRP polymorphisms are not significantly associated with MetS (OR = 0.92, 95% CI = 0.77-1.10) with significant heterogeneity (I 2 = 55.4%; p-value = 0.008). The subgroup analysis revealed that only GG has significant association with MetS (OR = 0.32, 95% CI = 0.13-0.80, p-value = 0.015) without significant heterogeneity (I 2 = 0%, p-value > 0.05). In conclusion, this meta-analysis provides strong evidence that only some SNPs of CRP gene are associated with the risk for development of MetS; and this relationship does not exist in different ethnic populations.
Published data on the relationship between pregnancy outcomes of preimplantation genetic diagnosis (PGD) in translocation carriers have implicated inconclusive results. To identify potentially eligible reports, an electronic search was conducted in several databases, including PubMed, Scopus, Web of Knowledge, and Cochrane. Pooled odd ratios (ORs) and 95% confidence intervals (Cis) were estimated based on a random-effect model to evaluate the strength of association between PGD and successful pregnancy outcome in translocation carriers. A total of six cohort studies were included in the current study. The meta-analysis of these studies revealed that the PGD method was associated with an increased successful pregnancy outcome of translocation carriers (OR = 8.58; 95%CI: 1.40-52.76). In subgroup analysis, there was no significant association according to the chromosomal translocation carrier origin and the type of translocated chromosomes, as well as country. In developed countries, the pregnancy outcome of PGD was significantly improved in translocation carriers (OR = 21.79; 95%CI: 1.93-245.52). The current meta-analysis demonstrated that the PGD method is associated with successful pregnancy outcome in both types of reciprocal and Robertsonian translocation carriers, especially in developed countries.
Cleft lip palate (CLP) is one of the common congenital anomalies with multifactorial etiology. Many genes are associated with its etiology. In one of the studies CRISPLD2 gene polymorphisms rs1546124, rs4783099, and rs16974880 were reported in the Chinese population. However, its role in the Indian population is not yet studied. Hence, this research was conducted on the Indian population to know the role of these high-risk polymorphisms in patients with nonsyndromic CLP. Following an inclusion and exclusion criteria, 20 multiplex CLP families were selected from a high volume cleft center in India. Genomic DNA was isolated from these families. Single nucleotide polymorphism (SNP) rs1546124, rs4783099, and rs16974880 were analyzed for their association using MassARRAY method. A whole-genome association analysis toolset, PLINK was used for statistical analysis. The polymorphisms followed Hardy-Weinberg equilibrium. None of the polymorphisms showed any significance. Hence the high-risk polymorphisms rs1546124, rs4783099, and rs16974880 are not associated with nonsyndromic CLP in Indian population.