Regulatory Role of Insulin on Endogenous L1 Orf1 and Nefm Gene Expression Through Pi3k Signaling Pathway Specifically in Neuroblastoma Cell Line



Sohrabi N¹ ; Habibi L¹ ; Akrami SM¹ Show Affiliations
Source: Iranian Journal of Public Health Published:2023

Abstract

Background: One of the most important endogenous factors causing genomic instability in human cells is L1s retrotransposons. In this study, we assume that increased activity of L1 retrotransposons (specifically L1 ex-pression) might be induced by hyperglycemia and hyperinsulinemia in neuroblastoma cell line. Methods: Two different cell lines (BE (2)-M17 and HEK293) were treated with insulin and its PI3K signaling pathway inhibitor under three conditional media including hyperglycemic and retinoic acid treatment in the department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran in 2018. The expression of L1 ORF1, as well as genes involved in insulin signaling pathway and neuronal stress and structure were measured at RNA level. Results: Insulin could significantly down regulate the expression of L1 ORF1 and NEFM genes. Hyperglyce-mia result in severe decrease in expression of all candidate genes in control neuroblastoma but not HEK293 cells. Retinoic acid as the concentration used in this study cause increase stemness in neuroblastoma but not HEK293 cells. We could not find significant correlation between expression pattern of other genes tested in our study and L1 ORF1 expression. Conclusion: Total regulatory effect of insulin on L1 ORF1 RNA expression as well as NEFM markedly in BE (2)-M17 cell line. Although these results could not be interpreted as L1 retrotransposition, expression of L1 RNA during stress conditions might be considered following inhibition of the insulin pathway. The result of this study also confirms the impotence of insulin on human evolution. © 2023 Sohrabi et al. Published by Tehran University of Medical Sciences..