Bioinformatics Analysis Reveals Novel Differentially Expressed Genes Between Ectopic and Eutopic Endometrium in Women with Endometriosis.

Background: Endometriosis is one of the chronic and prevalent diseases among women. There is limited knowledge about its pathophysiology at the cellular and molecular levels, causing a lack of a definite cure for this disease. In this study, differentially expressed genes (DEGs) between ectopic and paired eutopic endometrium in women with endometriosis were analyzed through bioinformatics analysis for better understanding of the molecular pathogenesis of endometriosis. Methods: Gene expression data of ectopic and paired eutopic endometrium were taken from the Gene Expression Omnibus database. DEGs were screened by the Limma package in R with considering specific criteria. Then, the protein-protein interaction network was reconstructed between DEGs. The fast unfolding clustering algorithm was used to find sub-networks (modules). Finally, the three most relevant modules were selected and the functional and pathway enrichment analyses were performed for the selected modules. Results: A total of 380 DEGs (245 up-regulated and 135 down-regulated) were identified in the ectopic endometrium and compared with paired eutopic endometrium. The DEGs were predominantly enriched in an ensemble of genes encoding the extracellular matrix and associated proteins, metabolic pathways, cell adhesions and the innate immune system. Importantly, DPT, ASPN, CHRDL1, CSTA, HGD, MPZ, PED1A, and CLEC10A were identified as novel DEGs between the human ectopic tissue of endometrium and its paired eutopic endometrium. Conclusion: The results of this study can open up a new window to better understanding of the molecular pathogenesis of endometriosis and can be considered for designing new treatment modalities.

The effects of FTO gene rs9939609 polymorphism on the association between breast cancer and dietary intake.

Breast cancer (BC) is the leading cause of cancer-related deaths in females worldwide and is related to genetic and environmental factors. Dietary components may strongly influence the risk of BC. A possible association was also reported between the fat mass and obesity-associated (FTO) single-nucleotide polymorphisms (SNPs) and BC. This study aimed to investigate the impact of FTO rs9939609 polymorphism on the association between BC and dietary intake. This study was conducted on 180 women with BC as the case group and 360 healthy women as the control group. The dietary intakes were assessed by a valid 168-item food frequency questionnaire (FFQ). The FTO gene was genotyped for rs9939609 polymorphism. After adjusting the confounding variables, there was no significant association between dietary intake and BC in individuals without risk allele. A positive association between dietary intake of omega-6 fatty acids and BC was found only in individuals with risk allele of FTO gene (OR: 1.31, 95% CI: 1.08-1.60, p: 0.006). FTO gene risk allele may influence the effect of diet on breast cancer risk. Further studies are needed to assess the possible effects of the FTO genotype on the association between BC risk and dietary components.

The effect of FTO rs9939609 polymorphism on the association between colorectal cancer and dietary fiber.

Background: Gene polymorphisms may explain the controversy on the association between colorectal cancer (CRC) and dietary fibers. The purpose of this study was to investigate the effect of fat mass and obesity-associated (FTO) rs9939609 polymorphism on the association between colorectal cancer and dietary fiber. Methods: This case-control study was conducted on 160 CRC cases and 320 healthy controls in Tehran, Iran. The participants' food intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). The frequency of rs9939609 FTO polymorphism in the case and control groups was determined using the tetra-primer amplification refractory mutation (tetra-ARMS) method. Results: In the participants with the TT genotype of the FTO rs9939609, the cases had higher BMI and lower intake of dietary fiber compared to the controls (P = 0.01). Among A allele carriers of FTO rs9939609 polymorphism, the cases had higher BMI (P = 0.04) and lower intake of total fiber (P = 0.02) and soluble fiber (P = 0.02). An inverse association was found between CRC and dietary fiber intake among those with the AA/AT FTO rs9939609 genotype after adjusting for age, sex, smoking, alcohol consumption, physical activity, BMI, and calorie intake (OR = 0.9, CI 95%:0.84-0.92, P < 0.05). Conclusion: This study found a link between higher dietary fiber consumption and a lower risk of CRC in A-allele carriers of FTO rs9939609 polymorphism. Future studies are needed to identify the underlying mechanisms of the association between CRC and dietary fibers in people with different FTO genotypes.

A comprehensive bioinformatic analysis revealed novel MicroRNA biomarkers of Parkinson's disease.

Parkinson's disease (PD) is categorized as a neurodegenerative disorder. Different studies have focused on the role of microRNAs (miRNAs) on PD progression. Due to its complexity in initiation and progression, a considerable requirement has arisen to identify novel miRNA biomarkers in a noninvasive manner. In silico analysis has been used to select differentially expressed miRNAs (DE-miRNAs) and key pathways in this disease. In this manner, several data sets of different neurodegenerative diseases have been analyzed to purify the findings of the present study. Totally, 15 DE miRNAs showed significant changes compared to healthy controls and other neurodegenerative diseases. Then, the targets of the miRNAs were predicted through miRTarBase and TargetScan databases. Besides, enrichment analysis was implemented for predicted target genes. Most of the target genes were enriched in the TRAIL signaling pathway, Regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism, protein serine/threonine kinase activity, and Cytoplasm. Moreover, a protein-protein interaction network was constructed to find the most key DE miRNAs and targets in this disease. The results of the present study may help researchers shed light on the discovery of novel biomarkers for PD.

Unraveling the Complex Interactions between the Fat Mass and Obesity-Associated (FTO) Gene, Lifestyle, and Cancer.

Carcinogenesis is a complicated process and originates from genetic, epigenetic, and environmental factors. Recent studies have reported a potential critical role for the fat mass and obesity-associated (FTO) gene in carcinogenesis through different signaling pathways such as mRNA N6-methyladenosine (m6A) demethylation. The most common internal modification in mammalian mRNA is the m6A RNA methylation that has significant biological functioning through regulation of cancer-related cellular processes. Some environmental factors, like physical activity and dietary intake, may influence signaling pathways engaged in carcinogenesis, through regulating FTO gene expression. In addition, people with FTO gene polymorphisms may be differently influenced by cancer risk factors, for example, FTO risk allele carriers may need a higher intake of nutrients to prevent cancer than others. In order to obtain a deeper viewpoint of the FTO, lifestyle, and cancer-related pathway interactions, this review aims to discuss upstream and downstream pathways associated with the FTO gene and cancer. The present study discusses the possible mechanisms of interaction of the FTO gene with various cancers and provides a comprehensive picture of the lifestyle factors affecting the FTO gene as well as the possible downstream pathways that lead to the effect of the FTO gene on cancer.

Interactions of Colorectal Cancer, Dietary Fats, and Polymorphisms of Arachidonate Lipoxygenase and Cyclooxygenase Genes: A Literature Review.

Objective: Genetics and dietary factors play important roles in the development of colorectal cancer (CRC). However, the underlying mechanisms of the interactions between CRC, gene polymorphisms, and dietary fat are unclear. This review study investigated the effects of polymorphisms of arachidonate lipoxygenase (ALOX) and cyclooxygenase (COX) genes in the association between CRC and dietary fat. Methods: All the related papers published from 2000 to 2022 were collected from different databases such as PubMed, Science Direct, Scopus, and Cochran using related keywords such as colorectal cancer, ALOX, COX, polymorphism, and dietary fat. Non-English and unrelated documents were excluded. Results: Some single-nucleotide polymorphisms (SNPs) in the ALOX and COX genes, such as rs2228065, rs6413416, and rs4986832 in the ALOX gene, and rs689465 in the COX gene may play significant roles in the association between the risk of CRC and dietary fats. SNPs of ALOX and COX genes may influence the effects of dietary fatty acids on the risk of CRC. Conclusion: Some polymorphisms of the ALOX and COX genes may have important roles in the effects of dietary fat on the risk of CRC. If future studies confirm these results, dietary recommendations for preventing colorectal cancer may be personalized based on the genotype of the ALOX and COX genes.