Ectopic miR-975 induces CTP synthase directed cell proliferation and differentiation in Drosophila melanogaster
| Autor: | Ghows Azzam, Wai Kan Woo, Shallinie Thangadurai, Najat Dzaki |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Gene isoform Male Cellular differentiation lcsh:Medicine Germline Article 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Spermatocytes Testis Melanogaster Animals Drosophila Proteins Carbon-Nitrogen Ligases Stem Cell Niche lcsh:Science Cytoskeleton Cell Proliferation Multidisciplinary biology lcsh:R Cell Differentiation biology.organism_classification Phenotype Cell biology Isoenzymes MicroRNAs 030104 developmental biology Drosophila melanogaster lcsh:Q 030217 neurology & neurosurgery Immunostaining |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-14 (2019) |
| ISSN: | 2045-2322 |
| Popis: | CTP synthase (CTPSyn) is an essential metabolic enzyme, synthesizing precursors required for nucleotides and phospholipids production. Previous studies have also shown that CTPSyn is elevated in various cancers. In many organisms, CTPSyn compartmentalizes into filaments called cytoophidia. In Drosophila melanogaster, only its isoform C (CTPSynIsoC) forms cytoophidia. In the fruit fly’s testis, cytoophidia are normally seen in the transit amplification regions close to its apical tip, where the stem-cell niche is located, and development is at its most rapid. Here, we report that CTPSynIsoC overexpression causes the lengthening of cytoophidia throughout the entirety of the testicular body. A bulging apical tip is found in approximately 34% of males overexpressing CTPSynIsoC. Immunostaining shows that this bulged phenotype is most likely due to increased numbers of both germline cells and spermatocytes. Through a microRNA (miRNA) overexpression screen, we found that ectopic miR-975 concurrently increases both the expression levels of CTPSyn and the length of its cytoophidia. The bulging testes phenotype was also recovered at a penetration of approximately 20%. However, qPCR assays reveal that CTPSynIsoC and miR-975 overexpression each provokes a differential response in expression of a number of cancer-related genes, indicating that the shared CTPSyn upregulation seen in either case is likely the cause of observed testicular overgrowth. This study presents the first instance of consequences of miRNA-asserted regulation upon CTPSyn in D. melanogaster, and further reaffirms the enzyme’s close ties to germline cells overgrowth. |
| Databáze: | OpenAIRE |
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