ABSTRACT
Tumor microenvironment is characterized by the occurrence of significant changes due to disrupted signaling pathways that affect a broad spectrum of cellular activities such as proliferation, differentiation, signaling, invasiveness, migration, and apoptosis. Similarly, a downregulated suppressor of cytokine signaling 3 (SOCS3) promotes increased JAK/STAT function due to aberrant cytokine signaling, which results in increased cell proliferation, differentiation, and migration. Multiple carcinomas including breast cancer, prostate cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer involve the disruption of SOCS3 expression due to microRNA overexpression. MicroRNAs are small, conserved, and non-coding RNA molecules that regulate gene expression through post-transcriptional inhibition and mRNA destabilization. The aim of this study was to identify putative microRNAs that interact with SOCS3 and downregulate its expression. In this study, miRWalk, TargetScan, and miRDB were used to identify microRNAs that interact with SOCS3, whereas RNA22 was utilized to identify the binding sites of 238 significant microRNAs. The tertiary structures of shortlisted microRNAs and SOCS3 regions were predicted through MC Sym and RNAComposer, respectively. For molecular docking, HDOCK was used, which predicted 80 microRNA-messengerRNA complexes and the interactions of the top 5 shortlisted complexes were assessed. The complexes were shortlisted on the basis of least binding affinity score and maximum confidence score. This study identifies the interactions of known (miR-203a-5p) and novel (miR-6756-5p, miR-6732-5p, miR-1203, miR-6887-5p) microRNAs with SOCS3 regions due to their maximum interactions. Identifying the interactions of these microRNAs with SOCS3 will significantly advance the understanding of oncomiRs (miRNAs that are associated with cancer development) in tumor development due to their influence on SOCS3 expression. These insights will assist in future studies to understand the significance of miRNA-SOCS3-associated tumor development and progression.
ABSTRACT
Background and Objectives: The study aimed to investigate whether Achromobacter mucicolens IA strain biofilm formation, which contributes to antibiotic resistance, could be enhanced by readily available nutrient sources like carbohydrates and environmental factors such as pH and NaCl. Additionally, the study aimed to identify any inherent genes that support biofilm formation in this strain, which is an opportunistic pathogen that affects immunocompromised patients and is resistant to many antibiotics. Materials and Methods: Biofilm growth in different carbohydrate, pH, and NaCl concentrated media was measured using crystal violet microtiter assay. All the treatments were subjected to biostatistics analysis for normality, Test of Homogeneity, one way ANOVA analysis. Whole-genome sequencing of our IA strain was conducted to identify various gene sequences. Results: Biofilm formation was measured at different carbohydrate concentrations, and the optimum biofilm formation was observed at 3M glucose and 0.5M NaCl, while the lowest results were seen at 2M maltose concentration. Whole-genome sequencing identified potential genes involved in biofilm formation, pathogenicity, protein metabolism, flagellar motility, cell wall component synthesis, and a multidrug efflux pump. Conclusion: These findings suggest that biofilm formation is influenced by extrinsic and intrinsic factors, which could aid in the development of effective treatments for resistant infections.
