MiR-137: an important player in neural development and neoplastic transformation

Abstract

MicroRNAs (miRNAs) represent an important class of small regulatory RNAs that control gene expression posttranscriptionally by targeting mRNAs for degradation or translation inhibition. Early studies have revealed a complex role for miRNAs in major biological processes such as development, differentiation, growth and metabolism. MiR-137 in particular, has been of great interest due to its critical role in brain function and putative involvement in the etiology of both neuropsychiatric disorders and cancer. Several lines of evidence suggest that development, differentiation and maturation of the nervous system is strongly linked to the expression of miR-137 and its regulation of a large number of downstream target genes in various pathways. Dysregulation of this molecule has also been implicated in major mental illnesses through its position in a variant allele highly associated with schizophrenia in the largest mega genome-wide association studies. Interestingly, miR-137 has also been shown to act as a tumor suppressor, with numerous studies finding reduced expression in neoplasia including brain tumor. Restoration of miR-137 expression has also been shown to inhibit cell proliferation, migration and metastasis, and induce cell cycle arrest, differentiation and apoptosis. These properties of miR-137 propose its potential for prognosis, diagnosis and as a therapeutic target for treatment of several human neurological and neoplastic disorders. In this review, we provide details on the discovery, targets, function, regulation and disease involvement of miR-137 with a broad look at recent discovery in this area.

Increased miR‐34c mediates synaptic deficits by targeting synaptotagmin 1 through ROS‐JNK‐p53 pathway in Alzheimer’s Disease

“…MicroRNAs (miRNAs) are small, endogenous, noncoding RNAs that negatively regulate gene expression at the post‐transcriptional level by binding to the “seed region” located in the 3’‐untranslated region (3’‐UTR) of their target mRNA (Mahmoudi & Cairns, ). MiRNAs are considered as a group of regulators in various biological processes, such as cell proliferation, differentiation, apoptosis, and cycle regulation (Bhaskaran et al, ; Mansini et al, ; Nowakowski et al, ).…”

“…Recently, some epidemiological researches have reported the negative association between AD and cancer, which means older persons with AD dementia have a reduced risk of cancer and vice versa (Calderwood & Murshid, 2017;Nixon, 2017;Shafi, 2016). Following studies have demonstrated that many factors, including miRNAs, are involved in the inverse relationship between AD and cancer (Nagaraj, Zoltowska, Laskowska-Kaszub, & Wojda, 2019 MicroRNAs (miRNAs) are small, endogenous, noncoding RNAs that negatively regulate gene expression at the post-transcriptional level by binding to the "seed region" located in the 3'-untranslated region (3'-UTR) of their target mRNA (Mahmoudi & Cairns, 2017).…”

Small nucleolar RNA host gene 1 promotes development and progression of colorectal cancer through negative regulation of miR‐137

“…miR‐137 is located on human chromosome 1p22 and is involved in many biological processes and diseases . To date, research indicates that miR‐137 may play a dual role during tumorigenesis, and that the nature of this role may be dependent on tumor type and target messenger RNA (mRNA) identities .…”

Dysregulation of miRNA and its potential therapeutic application in schizophrenia

“…miRNAs were predicted to regulate 20%‐30% of human genes . The involvement of miRNAs in many aspects of psychiatric disorder makes them potential candidates as biomarkers or targets for clinical diagnosis and treatment . Although the importance of miRNAs in brain functions has been well‐documented, more efforts are required to understand the full extent of miRNA regulatory mechanism and their pathological effects in neuropsychiatric disorders.…”

“…147,148 The involvement of miRNAs in many aspects of psychiatric disorder makes them potential candidates as biomarkers or targets for clinical diagnosis and treatment. 6,7,9,149 Although the importance of miRNAs in brain functions has been welldocumented, more efforts are required to understand the full extent of miRNA regulatory mechanism and their pathological effects in neuropsychiatric disorders. The first challenge remained is to identify functional miRNAs located in human genome associated with schizophrenia.…”