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Cell Journal، جلد ۲۰، شماره ۳، صفحات ۳۴۰-۳۴۷
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عنوان انگلیسی LRSAM1 Depletion Affects Neuroblastoma SH-SY5Y Cell Growth and Morphology: The LRSAM1 c.2047-1G>A Loss-of- Function Variant Fails to Rescue The Phenotype
چکیده انگلیسی مقاله Objective: LRSAM1 is a RING finger ubiquitin ligase, mutations in which have recently been associated with Charcot-Marie-Tooth disease (CMT2P). The mechanism through which mutated LRSAM1 contributes to the development of neuropathy is currently unclear. Materials and methods: In this experimental study we investigated the effect of LRSAM1 downregulation on neuroblastoma SH-SY5Y cells, using siRNA technology. Downregulation was performed with transfection of siRNA against LRSAM1. An equal dosage of WT or mutant LRSAM1 constructs were transfected in LRSAM1 downregulated cells to investigate the effect on the phenotype of the cells and whether cell proliferation and morphology could be rescued. Results: A significant reduction of TSG101 levels was observed with downregulation of LRSAM1. In addition, LRSAM1 knockdown significantly decreased the growth rate of neuroblastoma SH-SY5Y cells that is caused by a decrease of cell proliferation. An effect on the morphology of the neuroblastoma cells was also observed. Furthermore, we overexpressed wild-type (WT) and c.2047-1G>A mutant LRSAM1 in knockdown cells. WT LRSAM1 recovered the proliferation and partly the morphology of the cells, whereas, the c.2047-1G>A mutant did not recover cell proliferation and further aggravated the observed changes in cell morphology. Conclusion: Our findings prove that depletion of LRSAM1 affects neuroblastoma cells growth and morphology and that overexpression of the c.2047-1G>A mutant, unlike WT LRSAM1, fails to rescue the phenotype.
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نویسندگان مقاله | Anna Minaidou


| Paschalis Nicolaou


| Kyproula Christodoulou


نشانی اینترنتی http://celljournal.org/journal/article/abstract/5352
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