Abstract
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.
Highlights
One of the many hindrances to the discovery of a common cure for cancer is in the disease’s inherent complexity
CTPSynIsoC would cause in testicular tissue when it is expressed under the influence of a strong, ubiquitous Actin5C driver
In such situations where www.nature.com/scientificreports adjacent to the hub cells are phenotypically normal in CTPSynIsoC-overexpressing testis (B’ and B”). (C–C”) Control testis and (D–D”) Actin5C-GAL4 > UAS-CTPSynIsoC testis stained with anti-Vasa and anti-HTS
Summary
One of the many hindrances to the discovery of a common cure for cancer is in the disease’s inherent complexity. Several studies have shown a correlative relationship between CTPSyn cellular concentration to the length of cytoophidia[12,13] Under conditions whereby it is excessively available, the structure tends to become elongated[9], whereas the opposite is true if its gene is knocked-out or mutated. This dynamism exhibited by the cytoophidium in response to surrounding changes means that it could, at the very least, serve as an indicator for normal levels of cellular nucleotide production, especially in tissues where it could be found consistently and in relatively high numbers. Multiple drugs have been developed with the intention of attenuating the enzyme adequately enough to combat cancer progression[22,23,24]
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