Dendrosomal Curcumin Upregulates Expression of the Long Non-coding RNA gene MEG۳ in U۸۷MG Glioblastoma Cells

Objective:Glioblastoma is an invasive tumor of the central nervous system. Epigenetic therapy of cancer is potentially very useful in reversing some of cancer defects due to reversibility of epigenetic alterations. MEG۳ is a tumor suppressor long non-coding RNA (lncRNA) that expresses in the majority of normal tissues. Methylation of the MEG۳ promoter region elicits a decrease in its expression in glioblastoma cells. Bioactive nutrients including curcumin offer great potential in altering DNA methylation status. Herein, we aim to investigate the epigenetic-based role of dendrosomal-curcumin (DNC) in upregulation of MEG۳ expression in glioblastoma cells. Methods: We evaluated DNC entrance to U۸۷MG cells with the use of the fluorescent characteristics of curcumin. Next we performed the MTT assay to evaluate DNC and dendrosome effects on cell viability. The ability of DNC to boost expression of MEG۳ in DNA methylation regulation was accomplished by a study of the relative expressions of MEG۳ and DNA methylation regulator enzymes, DNA methyltransferases (DNMT۱, DNMT۳A and ۳B)  using semi-quantitative and quantitative PCR. Results: We observed the entrance of DNC into U۸۷MG cells. DNC significantly caused U۸۷MG cell death in a time and dose-dependent manner. However dendrosome did not show any toxic effect on this cell line. Data acquired from gene expression assays determined that DNC upregulated MEG۳ expression (P<۰.۰۵) and downregulated DNMT۳B expression (P<۰.۰۵). There was no significant effect on DNMT۱, ۳A expression in U۸۷MG cells. Conclusion: The data showed that DNC could awaken epigenetically silenced tumor suppressor genes through an ambiguous route in glioblastoma cells. Notwithstanding, DNA hypomethylation has occurred by downregulation of DNMTs, inactive DNA demethylation and or active demethylation, subsequently tumor suppressor genes such as MEG۳ a cell growth regulator overexpressed. We concluded that DNC has useful characteristics in epigenetic therapy of glioblastoma.

کلیدواژه ها:

MEG۳ ، Epigenetic ، Glioblastoma ، DNC ، MEG۳ ، DNMT ، گلیوبلاستوما ، کورکومین دندروزومی ، اپیژنتیک ، DNA متیل ترانسفراز