Estrogen-related receptor α (ESRRA) functions as a transcription factor and regulates the expression of several genes, such as WNT11 and OPN. Up-regulation of ESRRA has been reported in several cancers. However, the mechanism underlying its up-regulation is unclear. Furthermore, the reports regarding the role and regulation of ESRRA in oral squamous cell carcinoma (OSCC) are completely lacking. Here, we show that tumor suppressor miR-125a directly binds to the 3′UTR of ESRRA and represses its expression. Overexpression of miR-125a in OSCC cells drastically reduced the level of ESRRA, decreased cell proliferation, and increased apoptosis. Conversely, the delivery of an miR-125a inhibitor to these cells drastically increased the level of ESRRA, increased cell proliferation, and decreased apoptosis. miR-125a-mediated down-regulation of ESRRA impaired anchorage-independent colony formation and invasion of OSCC cells. Reduced cell proliferation and increased apoptosis of OSCC cells were dependent on the presence of the 3′UTR in ESRRA. The delivery of an miR-125a mimic to OSCC cells resulted in marked regression of xenografts in nude mice, whereas the delivery of an miR-125a inhibitor to OSCC cells resulted in a significant increase of xenografts and abrogated the tumor suppressor function of miR-125a. We observed an inverse correlation between the expression levels of miR-125a and ESRRA in OSCC samples. In summary, up-regulation of ESRRA due to down-regulation of miR-125a is not only a novel mechanism for its up-regulation in OSCC, but decreasing the level of ESRRA by using a synthetic miR-125a mimic may have an important role in therapeutic intervention of OSCC and other cancers. Estrogen-related receptor α (ESRRA) functions as a transcription factor and regulates the expression of several genes, such as WNT11 and OPN. Up-regulation of ESRRA has been reported in several cancers. However, the mechanism underlying its up-regulation is unclear. Furthermore, the reports regarding the role and regulation of ESRRA in oral squamous cell carcinoma (OSCC) are completely lacking. Here, we show that tumor suppressor miR-125a directly binds to the 3′UTR of ESRRA and represses its expression. Overexpression of miR-125a in OSCC cells drastically reduced the level of ESRRA, decreased cell proliferation, and increased apoptosis. Conversely, the delivery of an miR-125a inhibitor to these cells drastically increased the level of ESRRA, increased cell proliferation, and decreased apoptosis. miR-125a-mediated down-regulation of ESRRA impaired anchorage-independent colony formation and invasion of OSCC cells. Reduced cell proliferation and increased apoptosis of OSCC cells were dependent on the presence of the 3′UTR in ESRRA. The delivery of an miR-125a mimic to OSCC cells resulted in marked regression of xenografts in nude mice, whereas the delivery of an miR-125a inhibitor to OSCC cells resulted in a significant increase of xenografts and abrogated the tumor suppressor function of miR-125a. We observed an inverse correlation between the expression levels of miR-125a and ESRRA in OSCC samples. In summary, up-regulation of ESRRA due to down-regulation of miR-125a is not only a novel mechanism for its up-regulation in OSCC, but decreasing the level of ESRRA by using a synthetic miR-125a mimic may have an important role in therapeutic intervention of OSCC and other cancers. Withdrawal: MicroRNA-125a reduces proliferation and invasion of oral squamous cell carcinoma cells by targeting estrogen-related receptor α: Implications for cancer therapeutics.Journal of Biological ChemistryVol. 294Issue 15PreviewVOLUME 289 (2014) PAGES 32276–32290 Full-Text PDF Open Access
Montelukast sodium is a leukotriene receptor antagonist (LTRA) used for the maintenance treatment of asthma and to relieve symptoms of seasonal allergies 1-2 .Montelukast comes as a tablet, a chewable tablet, and granules to take by mouth 3 .Montelukast is usually taken once a day with or without food 3 .The present study describes a simple, accurate reproducible and precise uv spectrophotometric method for the estimation of Montelukast Sodium in bulk and in tablet dosage form.The absorbance maxima (λmax) for Montelukast Sodium were found to be 286.5nm.The method was validated for different parameters such as molar absorptivity, accuracy precision, ruggedness, robustness, detection limit, quantification limit etc, (as per ICH guidelines).The relative standard deviation (RSD) in case of, accuracy precision, ruggedness, robustness was less than 2.0% proving that method was highly accurate, precise and robust.This method can be used for determination of Montelukast Sodium in pharmaceutical formulations without interference of the excipients.
Synthetic biology is an emerging discipline of science, at the intersection of biology, engineering, and chemistry that involves redesigning organisms to have new phenotypes and customized abilities. While synthetic biology seems to have originated from genetic engineering, over the years, it has matured as well as diverged from it. It involves not just the transfer of genes from one or cell to another creating some variants, it also involves the assembly of an altogether novel organism or cell created part by part by the assembly of individual components of the desired function in a logical fashion. In this minireview, we will explore this new discipline and its possible applications and future promises to serve the humanity
Background: To study the efficacy of using maternal height, foot length, external pelvic measurements, sacral rhomboid dimensions as predictors of contracted pelvis (CP) in a cohort of our population and proposed to include estimated fetal weight as an additional parameter as a predictor of cephalopelvic disproportion. Methods: In 1000 uncomplicated primigravida after 37 weeks gestation, transverse and vertical diagonal (TD and VD) of the sacral rhomboid, intertrochanteric diameter, biacromial diameter, foot length in centimeters, height in centimeters and weight in kilograms and birth weight of the baby in kilograms were recorded. Postdelivery, patients fell into two groups: Group-1: control (no CP) - women having uncomplicated vertex vaginal delivery, Group-2: cases (CP) - this group will include women with pelvic disproportion having: Caesarean section for disproportion detected on pelvic assessment or for non-descent/non rotation of the fetal head, Vacuum or forceps delivery for prolonged second stage, Vaginal delivery complicated by obstruction, birth trauma or unexplained intrapartum asphyxia. These two groups will be compared for their outcome. Data was analyzed using t-test, Pearson's-Chi square, Fishers exact test and multivariant logistic regression. Results: Cephalopelvic disproportion was present in 123 women. In univariate analysis, maternal height, foot length, intertrochanteric diameter and biacromial diameter were found to be associated with cephalopelvic disproportion, Rhomboid dimensions were smaller in CP group (TD of rhomboid P value < 0.001, VD of rhomboid P value 0.001). For transverse diagonal, when the 10th percentile (
Genomic imprinting is an epigenetic chromosomal modification in the gametes or zygotes that results in a non-random monoallelic expression of specific autosomal genes depending upon their parent of origin. Approximately 44 human genes have been reported to be imprinted. A majority of them are clustered, including some on chromosome segment 11p15.5. We report here the imprinting status of the SLC22A1LS gene from the human chromosome segment 11p15.5In order to test for allele specific expression patterns, PCR primer sets from the SLC22A1LS gene were used to look for heterozygosity in DNA samples from 17 spontaneous abortuses using PCR-SSCP and DNA sequence analyses. cDNA samples from different tissues of spontaneous abortuses showing heterozygosity were subjected to PCR-SSCP analysis to determine the allele specific expression pattern. PCR-SSCP analysis revealed heterozygosity in two of the 17 abortuses examined. DNA sequence analysis showed that the heterozygosity is caused by a G>A change at nucleotide position 473 (c.473G>A) in exon 4 of the SLC22A1LS gene. PCR-SSCP analysis suggested that this gene is paternally imprinted in five fetal tissues examined.This study reports the imprinting status of the SLC22A1LS gene for the first time. The results suggest imprinting of the paternal allele of this gene in five fetal tissues: brain, liver, placenta, kidneys and lungs.
Mutations in PLA2G6 were identified in patients with a spectrum of neurodegenerative conditions, such as infantile neuroaxonal dystrophy (INAD), atypical late-onset neuroaxonal dystrophy (ANAD) and dystonia parkinsonism complex (DPC). However, there is no report on the genetic analysis of families with members affected with INAD, ANAD and DPC from India. Therefore, the main aim of this study was to perform genetic analysis of 22 Indian families with INAD, ANAD and DPC. DNA sequence analysis of the entire coding region of PLA2G6 identified 13 different mutations, including five novel ones (p.Leu224Pro, p.Asp283Asn, p.Arg329Cys, p.Leu491Phe, and p.Arg649His), in 12/22 (54.55%) families with INAD and ANAD. Interestingly, one patient with INAD was homozygous for two different mutations, p.Leu491Phe and p.Ala516Val, and thus harboured four mutant alleles. With these mutations, the total number of mutations in this gene reaches 129. The absence of mutations in 10/22 (45.45%) families suggests that the mutations could be in deep intronic or promoter regions of this gene or these families could have mutations in a yet to be identified gene. The present study increases the mutation landscape of PLA2G6. The present finding will be useful for genetic diagnosis, carrier detection and genetic counselling to families included in this study and other families with similar disease condition.
To carry out the mutation analysis of the KIF21A gene in a four-generation Indian family affected with CFEOM1 and to find out the molecular basis of the most frequent mutations c.2860C>T and c.2861G>A in exon 21 of the KIF21A gene.Mutational analysis was carried out by direct automated sequencing of the PCR products from exons 8, 20, and 21 of the KIF21A gene. Allele specific oligo hybridization analysis was carried out to study the segregation of the mutation within the family. Methylation status of the mutated CpG dinucleotide in exon 21 was detected using bisulfite genomic sequencing technique on genomic DNA isolated from blood and sperms.We found a previously reported missense mutation c.2860C>T (p.954R>W) in exon 21 of the KIF21A gene in our family. This mutation was found in a CpG dinucleotide. Bisulfite genomic sequencing revealed that all the CpG dinucleotides in exon 21 including the one which harbored the two most frequent mutations were methylated both in the genomic DNA from blood and sperms.CFEOM1 phenotype in our family was caused by a previously reported most frequent missense mutation, c.2860C>T. This mutation occurred at the C residue in a CpG dinucleotide, which was found to be methylated. Previous work has demonstrated that this CpG dinucleotide is a mutational hotspot in the KIF21A gene, and our finding suggests that its high mutability may result, in part, from its methylated state.
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