LncRNA DANCR Restrains Sensitivity to 5-fluorouracil in Prostate Cancer through Sponging MiR-577

ABSTRACT This present study explored the functions of lncRNA DANCR on regulating sensitivity to 5-fluorouracil (5- FU) in prostate cancer in vitro. The RT-qPCR examined RNA expressions of LNCRNA DANCR in RWPE-1, VCaP, PC3 and LNCaP cells, which also measured RNA levels of miR-577 in PC3 cells. DANCR was highly expressed in prostate cancer cell lines. 5-FU (0, 1, 5 and 10¼M) treatment induced the decrease of PC3 cell viability and low RNA expressions of DANCR but increased miR-577 in PC3 cells. The luciferase reporter test detected the binding between DNACR and miR- 577 . Interactions between DANCR and miR-577 were examined. Knockdown of DANCR downregulated DANCR and Bcl- 2 RNA expressions but accelerated cell viability and upregulated Bax, which were enhanced by the overexpression of miR- 577. Hence, DANCR might restrain sensitivity of prostate cancer cells to 5-FU by downregulating miR-577

MiR-382-5p’s Function as a Suppressor in Osteosarcoma (OS) by Targeting PDPK1

ABSTRACT miR-382-5p engages in development of osteosarcoma (OS). However, the regulatory system of miR-382-5p in osteosarcoma remains to be revealed. This research studied the interplay between PDPK1 and miR- 382-5p in OS. RT-PCR was used to evaluate miR-382-5p and PDPK1 expression in OS cells and normal human osteoblast cells. Dual-luciferase reporter assay validated PDPK1 as a miR-382-5p target. CCK-8 evaluated the cell viability. Flow cytometric method determined cell apoptosis rate. Transwell and Scratch assays estimated the cell metastasis. miR-382-5p was inhibited in OS cells. Further functional results showed miR-382-5p upregulation reduced cell viability, and mobility by mediating PDPK1 in OS cells

Identification of a Novel KRT9 Frameshift Mutation in a Chinese Pedigree with Epidermolytic Palmoplantar Keratoderma

Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant genodermatosis caused by variants of keratin 9 (KRT9) or KRT1 gene. In this study causative gene mapping in a Chinese EPPK family was performed with Two-point linkage analysis and haplotyping. Positive linkage results were obtained on 17q (Zmax=2.06, θmax=0.0) at D17S799, which indicated KRT9 to be the most responsible gene for the family. Subsequently, direct sequencing identified a novel frameshift mutation caused by a 5bp deletion (∆GGAGG) in KRT9 in all affected individuals but not in the unaffected members or the 50 unrelated controls. The frameshift changed the encoding of the following nine amino acids and resulted in a readthrough translation in exon 7. The data revealed that the novel frameshift mutation in KRT9 was responsible for the Chinese EPPK pedigree. The researchers’ findings broaden the spectrum of KRT9 variants and provide further evidence for the highly genetic heterogeneity of EPPK.

Predicting the Role of SERPINA1 DNA Methylation in Chronic Obstructive Pulmonary Disease and Anaemia and Identification of 3 Novel Methylation Sites

ABSTRACT Anaemia and chronic obstructive pulmonary disease (COPD) are the common blood and respiratory disorders respectively. The proper lung function is maintained by the SERPINA1 gene predominantly that encodes for alpha 1 antitrypsin protein, which also regulates the iron homeostasis of the human body, whereas imbalance in the iron homeostasis may result in the anaemic condition. The altitudinal variations influence anaemia and COPD. DNA methylation is involved in the early developmental processes, which influences the gene functioning without altering the sequence. The current study has been aimed at analyzing the inter-relationship between anaemia and COPD with DNA methylation of the SERPINA1 gene under altitudinal changes. The methodology involves the DNA isolation, bisulfite conversion and sequencing of the SERPINA1 gene. The results of the current study have shown that SERPINA1 DNA methylation did not significantly involve anaemia and COPD irrespective altitudes, but 3 novel CpG sites cg94377701, cg94389678 and cg94389930 were identified in the SERPINA1 gene of anaemia and COPD patients.

Down Syndrome Survey in South Indian Population- Understanding Inheritance, Perceptions, Interventions and Diagnosis

ABSTRACT Down syndrome (DS) has been prevalent worldwide, for centuries now. Despite the fact that tremendous research has been done on DS ever since the early 1950s, most results obtained, are on the basis of etiological and demographic factors and predominantly of the western data. Every year in India, >30,000 children are born with DS. This survey has been done keeping the Indian population in mind and to analyze the outlook of parents having children with DS, understand the comorbidities and their management. The study was conceptualized to create an exhaustive and comprehensive questionnaire to study the pattern of inheritance of Trisomy 21, analyze influence and correlation of advanced maternal age, sex ratio, order of birth, hypothyroidism, common comorbidities, abortions, Attention deficit hyperactivity disorder (ADHD) and sleeping difficulties in individuals diagnosed with DS. 50 family triads were interviewed. The results showed that incidence of DS was more in males compared to females. The analysis revealed that mean maternal age of 25-28 years showed increased incidence of DS. 2.5 percent showed severe ID and 27.5 percent had severe ADHD symptoms, while 10-13 percent showed mild to moderate ADHD. The most and least prevalent comorbidity seen was the presence of heart disease (45%) and hearing impairment (10 percent) respectively. It was found that about 40 percent of parents strongly agreed to the idea that Genetic Counseling (GC) is helpful and wanted to reinforce it to others who find it difficult to cope up with their DS child.

Distribution of Selected Single Nucleotide Polymorphisms in the Brahmin, Rajput and Bania Populations of Jammu District of Jammu and Kashmir, North India

ABSTRACTA total of 461 randomly selected unrelated subjects belonging to three selected castes populations of Jammu district of Jammu and Kashmir (J&K) viz., the Brahmin, Rajput, and Bania were typed using standard PCRRFLP technique for a battery of five SNPs (Single Nucleotide Polymorphisms) namely NAT2, ADH2, PSCR, T2, and ALAD. The objective of the present study was to characterize these populations genetically and assess the degree of genetic differentiation and genetic affinities among them. The results revealed that the present caste populations were moderately differentiated (GST = 0.0105).The genetic distance analysis demonstrated that the Rajput and Bania were in close genetic affinities while the Brahmin population was somewhat distant. In conclusion, the present investigation documented the underlying genomic uniformity in the people of the Jammu district.

Distribution of Human-specific Alu InDel Polymorphisms in the Brahmin and Rajput Populations of Kangra District of Himachal Pradesh, North India

ABSTRACT The genetic constitution of two endogamous caste populations viz., the Brahmin (n=250) and Rajput (n=250) of Kangra district of the North Indian state of Himachal Pradesh was studied using six autosomal Alu InDel (insertion/deletion) markers viz., ACE, APO, PV92, CD4, PLAT, and TPA25 All markers were found to be polymorphic. Except for Alu APO and PV92 in the Rajput, genotype frequencies of other markers were in the Hardy-Weinberg equilibrium in both the populations. The average heterozygosity (H) was observed higher in the Brahmin (0.4134) compared to the Rajput (0.3809) and the degree of genic differentiation was low between them (GST =0.00898). The genetic distance analysis revealed close genetic affinities of the present Rajput population with the Gaddi Rajput and Gaddi Brahmin populations reported earlier from the district but the present Brahmin population was found distant from them.

MiR-200a-3p Accelerated Hypoxia/Reoxygenation Injury in HCM Cells by Enhancing IGF2R via Wnt/β-catenin Signalling Pathway

ABSTRACT The present study examined functions of miR-200a-3p accelerated progressions of HCM cells via IGF2R and Wnt/β-catenin signalling pathway after hypoxia/reoxygenation treatment in vitro. CCK-8 showed that cell viability of HCM was inhibited while apoptosis rates detected by flow cytometry were promoted in a time dependent manner after H/R (12 hours and 24 hours). Beyond that, Bcl-2 and c-IAP1 were decreased but Bax and caspase-3 were upregulated by H/R treatment. IL-1β, IL-6, TNF-α and NLRP3 were also increased after treatment. RT-qPCR showed increased expressions of miR-200a-3p by H/R treatment while its inhibitor elevated cell viability but depressed apoptosis rate and pro-inflammatory cytokines’ expressions. IGF2R was upregulated after H/R treatment and its downregulation magnified effects of suppressed miR-200a-3p. HIF-1α/Wnt/β -catenin signalling pathway was activated by miR-200a-3p and IGF2R while IWP-2 treatment abolished the activation of Wnt3a andβ -catenin, causing decreased apoptosis and pro-inflammatory cytokines’ expressions but accelerated the cell viability.

Association of SNP rs700519 in CYP19A1 Gene with Polycystic Ovary Syndrome (PCOS) Among Females of Quetta, Pakistan

ABSTRACT Polycystic Ovary Syndrome (PCOS) is endocrine reproductive disorder which causes oligomenorrhea/ amenorrhea, infertility, type II diabetes. The present study aims in CYP19A1 polymorphism rs700519 (C/T) identification that elevates androgen among PCOS females in Quetta, Pakistan. Cross-sectional study involved enrollment of 100 control and 100 affected females. Blood samples were collected for genetic and hormonal analysis. The samples were amplified via ARMS PCR and analyzed by sequencing. The frequency of CC genotype in control and PCOS group was 48 percent and 33 percent. For CT, it was 52 percent and 67 percent. In control group, the allele frequency for C and T was 0.74 and 0.26. In PCOS group, it was 0.67 and 0.33 for C and T, respectively. The Pearson Chi-Square p=0.031 (p<0.05) at 95% Confidence Interval inferred a significant difference between the observed genotypes. The study inferred that CT genotype is a risk factor for PCOS progression in the population of Quetta.

Association of SNP rs700519 in CYP19A1 Gene with Polycystic Ovary Syndrome (PCOS) Among Females of Quetta, Pakistan

ABSTRACT Polycystic Ovary Syndrome (PCOS) is endocrine reproductive disorder which causes oligomenorrhea/ amenorrhea, infertility, type II diabetes. The present study aims in CYP19A1 polymorphism rs700519 (C/T) identification that elevates androgen among PCOS females in Quetta, Pakistan. Cross-sectional study involved enrollment of 100 control and 100 affected females. Blood samples were collected for genetic and hormonal analysis. The samples were amplified via ARMS PCR and analyzed by sequencing. The frequency of CC genotype in control and PCOS group was 48 percent and 33 percent. For CT, it was 52 percent and 67 percent. In control group, the allele frequency for C and T was 0.74 and 0.26. In PCOS group, it was 0.67 and 0.33 for C and T, respectively. The Pearson Chi-Square p=0.031 (p<0.05) at 95% Confidence Interval inferred a significant difference between the observed genotypes. The study inferred that CT genotype is a risk factor for PCOS progression in the population of Quetta.