Unravelling the molecular mechanism of miR-۱۲۸ in oligodendrocyte differentiation

Backgrounds: Neurodegenerative diseases are regarded a major threat to human health. Theyare incurable and debilitating conditions leading to progressive degeneration of neurons and theirmyelin sheaths. So unravelling cellular and molecular aspects of myelin synthesis pathways arebasic importance in order to open new avenues for developing a cell-based therapy fordemyelinating neurodegenerative disorders such as multiple sclerosis. Among different micorRNAs with potential or proved roles in oligodendrocyte differentiation, exact molecularmechanism of miR-۱۸۴ is not yet well understood.Materials and Methods: We performed RT-PCT and western blotting to measure expressionlevel of mir-۱۸۴ in neural progenitors (NPs). Also, luciferase assay was performed to exploremir-۱۸۴ effects on genes involved in neural and astrocyte differentiation such as SOX۱ andBCL۲L۱. Moreover, we assessed oligodendrocyte differentiation after blocking mir-۱۸۴.Results: We observed that overexpression of miR-۱۸۴ in NPs can induce differentiation ofoligodendrocyte progenitors. Assessing the related genes involved in this pathway using theabove mentioned techniques, revealed that several crucial developmental genes are likelyaffected by miR-۱۸۴ and this miR directly represses positive regulators of neural and astrocytedifferentiation, i.e., SOX۱ and BCL۲L۱, respectively. Moreover, blocking miR-۱۸۴ diminishedthe number of committed cells to an oligodendrocyte lineage.Conclusion: We assessed the function of miR-۱۸۴ and observed that it could induceoligodendrocyte differentiation. Herein we propose a novel factor to improve oligodendrocytedifferentiation with outstanding potential effects in cell therapy of neurodegenerative diseases.

کلیدواژه ها:

miR-۱۸۴ ، Oligodendrocyte differentiation pathway ، Neurodegenerative disease