Neural Regeneration Research ›› 2022, Vol. 17 ›› Issue (11): 2325-2334.doi: 10.4103/1673-5374.338990

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Interplay of SOX transcription factors and microRNAs in the brain under physiological and pathological conditions

Milena Stevanovic1, 2, 3, *, Danijela Stanisavljevic Ninkovic1, Marija Mojsin1, Danijela Drakulic1, Marija Schwirtlich1   

  1. 1Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia; 2University of Belgrade, Faculty of Biology, Belgrade, Serbia; 3Serbian Academy of Sciences and Arts, Belgrade, Serbia
  • Online:2022-11-15 Published:2022-04-21
  • Contact: Milena Stevanovic, Academician, Professor, milenastevanovic@imgge.bg.ac.rs.
  • Supported by:
    This work was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (Agreement number 451-03-9/2021-14/200042, to MiS, DSN, MM, DD and MaS) and the Serbian Academy of Sciences and Arts (Grant number F24, to MiS (PI), MM, DD and MaS).

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Abstract: Precise tuning of gene expression, accomplished by regulatory networks of transcription factors, epigenetic modifiers, and microRNAs, is crucial for the proper neural development and function of the brain cells. The SOX transcription factors are involved in regulating diverse cellular processes during embryonic and adult neurogenesis, such as maintaining the cell stemness, cell proliferation, cell fate decisions, and terminal differentiation into neurons and glial cells. MicroRNAs represent a class of small non-coding RNAs that play important roles in the regulation of gene expression. Together with other gene regulatory factors, microRNAs regulate different processes during neurogenesis and orchestrate the spatial and temporal expression important for neurodevelopment. The emerging data point to a complex regulatory network between SOX transcription factors and microRNAs that govern distinct cellular activities in the developing and adult brain. Deregulated SOX/microRNA interplay in signaling pathways that influence the homeostasis and plasticity in the brain has been revealed in various brain pathologies, including neurodegenerative disorders, traumatic brain injury, and cancer. Therapeutic strategies that target SOX/microRNA interplay have emerged in recent years as a promising tool to target neural tissue regeneration and enhance neurorestoration. Numerous studies have confirmed complex interactions between microRNAs and SOX-specific mRNAs regulating key features of glioblastoma. Keeping in mind the crucial roles of SOX genes and microRNAs in neural development, we focus this review on SOX/microRNAs interplay in the brain during development and adulthood in physiological and pathological conditions. Special focus was made on their interplay in brain pathologies to summarize current knowledge and highlight potential future development of molecular therapies.

Key words: dysregulation of miRNA expression, glioblastoma, gliogenesis, glioma stem cells, ischemic stroke, neural stem cells, neural tissue regeneration, neurodegenerative diseases, neurodevelopment, neurogenesis, SOX/miRNA interplay, traumatic brain injury