A Perspective on the Role of microRNA-128 Regulation in Mental and Behavioral Disorders

Abstract

MiRNAs are short, non-coding RNA molecules that regulate gene expression post-transcriptionally. Over the past decade, misregulated miRNA pathways have been associated with various diseases such as cancer, neurodegenerative diseases, and neurodevelopmental disorders. In this article, we aim to discuss the role played by miR-128 in neuropsychiatric disorders, and highlight potential target genes from an in silico analysis of predicted miR-128 targets. We also discuss the differences of target gene determination based on a bioinformatics or empirical approach. Using data from TargetScan and published reports, we narrowed the miR-128 target gene list to those that are known to be associated with neuropsychiatric disorders, and found that these genes can be classified into 29 gene clusters and are mostly enriched in cancer and MAPK signaling pathways. We also highlight some recent studies on several of the miR-128 targets which should be investigated further as potential candidate genes for therapeutic interventions.

Identification of Diagnostic and Prognostic microRNAs for Recurrent Vitreous Hemorrhage in Patients with Proliferative Diabetic Retinopathy

“…Interestingly, the present data could not corroborate significant differential expression for certain miRNAs previously reported as associated with PDR [25,50,51]. miRNA-29a has been shown to be a negative regulator of DR and its decrease in expression levels is associated with exacerbation of PDR [25,51].…”

“…miRNA-128 regulates multiple pathways within the cell including pathways involved in cancer or neuronal maturation. It has been shown to have tumor suppression activity, and has received particular interest in neuroscience research as it is highly expressed in the cortex and cerebellum during development [50]. Detection of miRNA-128 expression in human vitreous is reported here for the first time, however, its relevance as a biomarker or molecular effector of ocular disease including PDR needs further study.…”

miR‐128 Regulates Genes Associated with Inflammation and Fibrosis of Rat Kidney Cells In Vitro

“…Besides, our results are consistent with that of Tan and colleagues (Tan et al, ), where miR‐128 was shown to be associated with MAPK and ERK pathways in neurons. Furthermore, Mapk14 has been previously reported to be one of the targets of miR‐128 in neurons (Ching and Ahmad‐Annuar, ).…”

“…miRNAs regulate one‐third of the human genes and thus control a host of cellular functions, that include fundamental processes such as cell differentiation, proliferation and apoptosis, as well as signaling pathways (Croce and Calin, ; Bueno and Malumbres, ; Li et al, ; Su et al, ). miRNA‐128 (miR‐128) is a highly conserved miRNA in human and rodent genomes, suggesting that it may regulate similar cellular functions (Ching and Ahmad‐Annuar, ). Although miR‐128 was identified as a tumor suppressor in breast cancer (Qian et al, ) and lung cancer (Weiss et al, ), nonetheless, it is also a brain‐enriched miRNA (Krichevsky et al, ; Smirnova et al, ), signifying that miR‐128 has diverse roles in human development and disease (Pandey et al, ).…”

“…miR‐128 has been shown to be associated with reactive oxygen species (ROS), inflammation, Mitogen‐Activated Protein Kinase (MAPK) pathway and fibrosis in many types of tissues. miR‐128 has also been reported to regulate the MAPK signaling pathway in neuropsychiatric disorders (Ching and Ahmad‐Annuar, ) and cancer (Chakraborty et al, ). Furthermore, miR‐128 has been shown to increase intracellular ROS in medulloblastoma (Venkataraman et al, ) and human embryonic HEK293T cells (Adlakha and Saini, ), as well as target the p38/MAPK pathway in neurons (Tan et al, ).…”