Ectopic miR-975 induces CTP synthase directed cell proliferation and differentiation in Drosophila melanogaster.
Wai Kan WooNajat DzakiShallinie ThangaduraiGhows AzzamPublished in: Scientific reports (2019)
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.
Keyphrases
- cell proliferation
- drosophila melanogaster
- poor prognosis
- induced apoptosis
- cell cycle
- cell cycle arrest
- pi k akt
- long non coding rna
- stem cells
- germ cell
- high throughput
- transcription factor
- oxidative stress
- binding protein
- papillary thyroid
- gene expression
- squamous cell carcinoma
- endoplasmic reticulum stress
- squamous cell
- bone marrow
- case control
- children with cerebral palsy
- fatty acid