Molecular Biology Research Communications最新文献

Prostate cancer is a disease that depends on androgenic stimulation and is thus commonly treated with androgen deprivation therapy (ADT). ADT is highly successful initially; however, patients inevitably relapse at which point the cancer grows independently of androgens and is termed castration-resistant prostate cancer (CRPC). CRPC develops through various mechanisms, one of these being crosstalk of the androgen receptor (AR) signaling pathway with other signaling pathways. Congruently, prior work has shown that androgen deprivation induces SHH signaling, which subsequently promotes activation of AR-dependent gene expression to promote cell growth. Mechanistically, this crosstalk involves a physical interaction between AR and components of SHH signaling, specifically proteins of the GLI transcription factor family. These findings thus suggest that activation of SHH signaling could promote the recurrence of cell growth in the absence of androgens to ultimately lead to progression towards CRPC. In this study, we have investigated this mechanism in a subset of prostate cancer that harbors genetic alterations within the Mediator subunit 12 (MED12). We found that loss of MED12 promotes the expression of GLI3 target genes which subsequently drives excessive cell growth in the absence of androgens. Thus, we conclude that genetic alterations within MED12 promote CRPC through hyperactivated GLI3 dependent sonic hedgehog signaling.

Neovascular age-related macular degeneration (nAMD) is a progressive ocular disease, responsible for central visual loss and blindness in elderly population. Increase data demonstrate that genetic factors play an important role in pathogenesis process of this disease. The aim of this study is to investigate the association between rs3732378 polymorphism in CX3CR1 gene and nAMD in a sample of Algerian patients. This case-control study consisted of 72 patients with nAMD and 124 control subjects. DNA of participants was extracted using salting out method. Genotyping was carried out using the TaqMan real-time polymerase chain reaction method. Statistical analysis was performed by SPSS.21.0. The prevalence of the risk genotype AA was higher in the nAMD group than in control group (OR=5.02, 95% CI=1.44-17.4, P=0.011). In our sample of Algerian patients, the rs3732378 polymorphism is associated with nAMD. This result may support the role of CX3CR1 gene in the pathogenesis of nAMD.

Epithelial-to-mesenchymal transition (EMT) plays a critical role in colorectal cancer (CRC) metastasis. In the present study, we evaluated the effects of annexin A5 (ANXA5) overexpression on invasiveness as well as the expression of genes involved in EMT of HCT 116 cell line. PCMV6-AC-IRES-GFP plasmid harboring ANXA5 cDNA was constructed. HCT 116 cell line was transfected with recombinant plasmids using Lipofectamine 3000. Fluorescent microscopy was used to determine the efficiency of plasmid transfection. Cell viability was determined using the MTT assay. HCT 116 cell migration was evaluated using wound healing assay and transwell migration assay. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression of genes involved in EMT. The results of RT-qPCR showed overexpression of ANXA5 compared to the control group. ANXA5 overexpression had no significant effects on cell viability but significantly decreased the rate of wound closure in the wound healing assay as well as the number of migrated cells in transwell assay. Furthermore, ANXA5 overexpression decreased the expression of N-cadherin, Snail, Slug, MMP-2, and MMP-9 while the expression of E-cadherin increased following ANXA5 overexpression. However, VEGF expression did not significantly change after ANXA5 overexpression. Results of the present study suggest that ANXA5 overexpression might have inhibitory effects on the metastasis of CRC through modulating the expression of EMT- related genes.

The present study aims to determine the association between a genetic polymorphism of GSTP1 (rs1695) and the risk of periodontitis. This study used a cross-sectional design and included subjects from the South Indian population. A total of 100 individuals enrolled at Saveetha Dental College and Hospital, Tamil Nadu were included in this study. The participants were divided into control (n=50) and periodontitis (n=50) based on clinical examination. Blood samples were collected. Genotyping was performed using specific primers spanning the polymorphic site. The genotypic frequencies for the rs1695 polymorphism were not significantly different between cases and controls.

Increasing evidence shows that polymorphisms in CFI and ARMS2 genes can influence exudative age-related macular degeneration (nAMD) risk. The aim of this study was to assess the role of CFI rs10033900 and ARMS2 rs3750846 polymorphisms in susceptibility to nAMD for the first time in the Algerian population. A total of one hundred twenty four controls and seventy two nAMD cases were included in the present study. Genomic DNA was extracted from venous blood leukocytes. CFI rs10033900 and ARMS2 rs3750846 variants were determined by using the real‑time polymerase chain reaction method. Differences in allele and genotype distribution between the cases and controls were tested with adjustment for age by logistic regression analysis. A stratification of case and control groups by age (<65 or ≥65) and by gender (male and female) was also performed. Statistical analyses were done using SPSS21.0. No statistically significant association was observed between CFI rs10033900 and ARMS2 rs3750846 polymorphisms and nAMD risk (p>0.05 for all comparisons). Stratification by age and gender did not show any significant association between these two polymorphisms and nAMD in a sample of the Algerian population. In our study, CFI rs10033900 and ARMS2 rs3750846 polymorphisms did not predispose alone to nAMD in our population. This study is a contribution to the enrichment of the bank data concerning the CFI and ARMS2 genes, reporting, for the first time, the allelic and genotypic frequencies of these genes polymorphisms characterizing the Algerian population.

Benign prostatic hyperplasia (BPH) is a commonly occurring disease in aging men. It involves cellular proliferation of stromal and glandular tissues leading to prostate enlargement. Current drug therapies show several adverse effects such as sexual dysfunctions and cardiovascular side effects. Therefore, there is a need to develop more effective medical treatment for BPH. In this regard, we aimed to identify genes which play a critical role in BPH. We have obtained the dataset of differentially expressed genes (DEGs) of BPH from NCBI GEO. DEGs were investigated in the context of their protein-protein interactions (PPI). Hub genes i.e. genes associated with BPH were scrutinized based on the topological parameters of the PPI network. These were analyzed for functional annotations, pathway enrichment analysis and transcriptional regulation. In total, 38 hub genes were identified. Hub genes such as transcription factor activator protein-1 and adiponectin were found to play key roles in cellular proliferation and inflammation. Another gene peroxisome proliferator activated receptor gamma was suggested to cause obesity, a common comorbidity of BPH. Moreover, our results indicated an important role of transforming growth factor-beta (TGF-β) signaling and smooth muscle cell proliferation which may be responsible for prostate overgrowth and associated lower urinary tract symptoms frequently encountered in BPH patients. Zinc finger protein Snai1 was the most prominent transcription factor regulating the expression of hub genes that participate in TGF-β signaling. Overall, our study has revealed significant hub genes that can be employed as drug targets to develop potential therapeutic interventions to treat BPH.

The Human endogenous retroviruses (HERVs) are ancient remnants of exogenous retroviral infections. Their abnormal activation is associated with several diseases, such as cancer and autoimmunity. Epigenetic and environmental factors are probably playing essential roles in the expression of these elements. This study aimed to examine the 96-hour effects of ELF-EMF on HERV-H, K, and W expression in human melanoma cells. SK-MEL-37 cells (the human skin malignant melanoma) were continuously exposed to ELF-EMF (50 Hz) at 1.5 and 3 mT intensity for 96 hours. Following mRNA extraction, the expression level of HERV-H, K, and W was assessed by qPCR. According to our results, exposure to ELF-EMF intensities for 96 hours could significantly downregulate HERV-H, K, and W env gene expression (P<0.001). Our obtained data suggest that low intensity and long-term exposure to ELF-EMF may pave using this type of radiation as a novel therapeutic approach by neutralizing the HERVs upregulated expression in melanoma cells.

tRNA modifications play a significant role in the structural stability as well as translational fidelity in all organisms from bacteria to humans. They also play a major role in bacterial physiology by regulating translation in response to various environmental stresses. Modifications coming at the anticodon-stem loop (ASL) are particularly important as they stabilize codon-anticodon interactions, ensuring accuracy and speed in decoding mRNAs Addition of isopentenyl group (i6A) at A37 position by tRNA isopentenyltransferase (MiaA) is a well conserved modification from bacteria to human. We studied M. tuberculosis MiaA from strain H37Rv and identified the target tRNAs for this modification based on the A36A37A38 motif. i6A modification of target tRNAs tRNA^LeuCAA, tRNA^PheGAA, tRNA^TrpCCA and tRNA^SerCGA were further confirmed by isopentenyltransferase assay providing the substrate DMAPP and recombinant MiaA enzyme.

Francisella tularensis is a pathogenic, aerobic gram-negative coccobacillus bacterium. It is the causative agent of tularemia, a rare infectious disease that can attack skin, lungs, eyes, and lymph nodes. The genome of F. tularensis has been sequenced, and ~16% of the proteome is still uncharacterized. Characterizations of these proteins are essential to find new drug targets for better therapeutics. In silico characterization of proteins has become an extremely important approach to determine the functionality of proteins as experimental functional elucidation is unable to keep pace with the current growth of the sequence database. Initially, we have annotated 577 Hypothetical Proteins (HPs) of F. tularensis strain SCHU4 with seven bioinformatics tools which characterized them based on the family, domain and motif. Out of 577 HPs, 119 HPs were annotated by five or more tools and are further screened to predict their virulence properties, subcellular localization, transmembrane helices as well as physicochemical parameters. VirulentPred predicted 66 HPs out of 119 as virulent. These virulent proteins were annotated to find the interacting partner using STRING, and proteins with high confidence interaction scores were used to predict their 3D structures using Phyre2. The three virulent proteins Q5NH99 (phosphoserine phosphatase), Q5NG42 (Cystathionine beta-synthase) and Q5NG83 (Rrf2-type helix turn helix domain) were predicted to involve in modulation of cytoskeletal and innate immunity of host, H2S (hydrogen sulfide) based antibiotic tolerance and nitrite and iron metabolism of bacteria. The above predicted virulent proteins can serve as novel drug targets in the era of antibiotic resistance.