MicroRNA function can be reversed by altering target gene expression levels

Abstract MicroRNAs (miRNAs) have been identified in many organisms, and they are essential for gene expression regulation in many critical cellular processes. The expression levels of these genes and miRNAs are closely associated with the progression of diseases such as cancers. Furthermore, survival analysis is a significant indicator for evaluating the criticality of these cellular processes in cancer progression. We established a web tool, miRNA Target Viewer (miR-TV), which integrates 5p-arm and 3p-arm miRNA expression profiles, mRNA target gene expression levels in healthy and cancer populations, and clinical data of cancer patients and their survival information. The developed miR-TV obtained miRNA-seq, mRNA-seq and clinical data from the Cancer Genome Atlas and potential miRNA target gene predictions from miRDB, targetScan and miRanda. The data presentation was implemented using the D3 javascript toolkit. The D3 toolkit is frequently used to provide an easy-to-use interactive interface. Our miR-TV provides a user-friendly and interactive interface, which can be beneficial for biomedical researchers to freely interrogate miRNA expression information and their potential target genes. We believe that such a data visualization bioinformatics tool is excellent for obtaining information from massive biological data. Database URL: http://mirtv.ibms.sinica.edu.tw

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SAT-726 Estrogen Receptor Alpha as a Potential Target for Bisphenol A-Mediated Epigenetic Reprogramming: An in Vitro Analysis

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.043 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Morgan Gallo ◽

Lindsey S Treviño ◽

Tiffany A Katz

Keyword(s):

Gene Expression ◽

Target Gene ◽

Target Genes ◽

Hepatic Cell ◽

Time Points ◽

Target Gene Expression ◽

Er Alpha ◽

Hepatic Cell Lines ◽

Gene Expression Levels

Abstract Perinatal exposure to bisphenol A (BPA) has been shown to reprogram the hepatic epigenome of rodents and may promote the development of various metabolic diseases later in life, such as nonalcoholic fatty liver disease (NAFLD). This developmental reprogramming is characterized by the creation of “super promoters” at target genes implicated in metabolic pathways. While it is unclear how these “super promoters” are created, their creation is potentially mediated through BPA and estrogen receptor (ER) interaction. In order to test this potential mechanism, in vitro methods were used to examine ER target gene expression via RT-qPCR in 2 human hepatic cell lines transiently transfected with the ER isoform, ER alpha, prior to BPA exposure for various lengths of time. Within individual time points, there were no significant differences in target gene expression levels between cells that had been transfected with ER alpha and the vector control. Gene expression levels in the target genes were visibly increased at the 24-hour exposure mark in both transfection groups in comparison to the 0- and 6-hour time points, however only a fraction of these increases were found to be statistically significant. These gene expression patterns are not only consistent with previous studies examining target gene expression in BPA-treated hepatic cell lines, but more importantly, suggest BPA does not act via ER alpha to orchestrate the epigenetic changes seen in vitro. BPA may interact with a different ER isoform or an unknown target to create the observed “super promoters” at target genes, reinforcing the promiscuity of BPA and other xenoestrogens in facilitating epigenetic modifications, and ultimately, disease phenotypes.

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Expression of Vitamin D Receptor Pathway Genes in Subcutaneous Adipose Tissue of Obese Individuals

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1342 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A658-A658

Author(s):

Olivia Z B Ginnard ◽

Stephanie Sisley

Keyword(s):

Gene Expression ◽

Vitamin D ◽

Vitamin D Deficiency ◽

Subcutaneous Adipose Tissue ◽

Target Gene ◽

The Body ◽

Target Gene Expression ◽

Vitamin D Levels ◽

Subcutaneous Adipose ◽

Gene Expression Levels

Abstract Introduction: Vitamin D deficiency is a substantial comorbidity in 50% of pediatric patients and is linked with poorer health outcomes in children. Vitamin D levels are also shown to be inversely related to BMI. Therefore, there are many more children with low vitamin D levels due to the increasing prevalence of pediatric obesity. Pediatric patients with obesity and vitamin D deficiency also have a uniquely increased risk of metabolic syndrome, as compared to their lean peers. Measured levels of vitamin D correlate with other physiological markers of vitamin D effects in lean individuals but not obese individuals. It is possible that vitamin D levels reflect a storage form of vitamin D rather than a true reflection of vitamin D action in the body in this particular population. The aim of this study was to provide foundational knowledge to understand if expression of vitamin D receptor (VDR)-target genes may be used as a reference standard for vitamin D status in the body. Methods: We performed a secondary analysis of samples obtained from 33 obese adolescents that were consented under a past IRB-approved protocol. They were between the ages of 13 to 18 years that underwent bariatric surgery between 2004 and 2019. Data comprised of age, gender, race/ethnicity, and BMI. Samples collected included blood and subcutaneous adipose tissue. The tissue was analyzed via Real Time-PCR to obtain quantitative levels of VDR-target gene expression, which included PPARg, TLR4, THBD, CYP24A1, and VDR. Gene expression levels were normalized to the average of two housekeeping genes, GAPDH and RPLPO. Blood samples provided vitamin D levels (serum 25(OH)D). Results: VDR-target gene expression was significantly correlated between THBD, VDR, and TLR4 (p <0.05), and PPARg with THBD and TLR4 (p <0.05). There was no correlation observed between CYP24A1 gene expression and the other genes that were evaluated (p >0.05). PPARg, THBD, TLR4, CYP24A1, and VDR gene expression levels did not correlate with circulating serum 25(OH)D levels (p >0.05). Conclusion: These preliminary findings suggest that VDR-target gene expression correlates with each other but not with circulating serum 25(OH)D levels. This discrepancy supports that 25(OH)D levels do not indicate levels of vitamin D action and may not be an appropriate indicator of vitamin D deficiency in the obese population. Also, the observed CYP24A1 gene expression was limited in subcutaneous adipose tissue yet expression was seen in multiple other VDR-target genes. This emphasizes the tissue-specific nature of gene regulation of vitamin D. Further work should investigate VDR-target gene expression levels across multiple tissues of obese individuals to determine if markers of vitamin D action in one tissue are reflective of action across the body. This study may provide the first step in determining a new and more accurate biomarker for vitamin D deficiency and treatment in obesity.

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