Abstract
Background
Genistein is an isoflavone and phytoestrogen originated from soybean and soy products. Due to the close structural and functional proximity towards 17β-estradiol, genistein has been suggested to influence endocrine and reproductive systems. Previous studies showed that genistein could affect hypothalamic–pituitary–gonadal (HPG) axis and impact gonadotropin-releasing hormone (GnRH) secretion in hypothalamic GT1-7 neurons. However, the underlying mechanism remains mostly unknown.
Objectives
Comparative transcriptomic analyses of mRNAs, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) were performed in genistein-treated GT1-7 cells by high-throughput RNA sequencing. Competing endogenous RNA (ceRNA) networks were constructed based on potential interactions in lncRNAs, miRNAs and mRNAs.
Results
Compared to the control, 1134, 1126 and 30 differentially expressed mRNA, lncRNA and miRNAs were identified. The most significantly upregulated mRNA was growth-regulating estrogen receptor binding 1 (Greb1), possibly related to the increased levels of estrogen receptors (Esr1 and Esr2). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses demonstrated that genistein interfered with cell cycle, metabolic processes, as well as GnRH and mitogen-activated protein kinase signaling pathways in GT1-7 cells. CeRNA networks predicted that prostatic cancer-related miRNA mmu-miR-212-5p and its targeted genes Phf2 and Aldh3b1 might be associated with the regulation of genistein-induced GnRH secretion in GT1-7 cells, and 27 lncRNAs could completely interact with mmu-miR-212-5p and downregulate the transcription of target genes.
Conclusion
Results from the study could provide potential targets of both mRNA and non-coding RNAs for further studies to explore the endocrine-interfering effects of genistein.
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Acknowledgements
This study was funded by Department of Science and Technology of Sichuan Province (Grant 2021YJ0156), the Study of Diet and Nutrition Assessment and Intervention Technology (No. 2020YFC2006300) from Active Health and Aging Technologic Solutions Major Project of National Key R&D Program, and the National Nature Science Foundation of China (Grant 82173512).
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JX, YT and GC designed the study. JX, YT, GM and AL conducted the experiments. JX and YT analyzed and interpreted the data. JX, SS and GC provided reagents. JX and AL prepared the manuscript. JX, SS and GC reviewed and revised the manuscript. All authors have read and approved the manuscript.
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JX states that there is no conflict of interest to disclose. YT states that there is no conflict of interest to disclose. GM states that there is no conflict of interest to disclose. AL states that there is no conflict of interest to disclose. SS states that there is no conflict of interest to disclose. GC states that there is no conflict of interest to disclose.
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Xiong, J., Tian, Y., Ma, G. et al. Comparative RNA-seq analysis and ceRNA network of genistein-treated GT1-7 neurons. Mol. Cell. Toxicol. 19, 499–507 (2023). https://doi.org/10.1007/s13273-022-00279-1
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DOI: https://doi.org/10.1007/s13273-022-00279-1