Long Non-coding RNA HOTAIR in Central Nervous System Disorders: New Insights in Pathogenesis, Diagnosis, and Therapeutic Potential

Abstract

Central nervous system (CNS) disorders, such as ischemic stroke, neurodegenerative diseases, multiple sclerosis, traumatic brain injury, and corresponding neuropathological changes, often lead to death or long-term disability. Long non-coding RNA (lncRNA) is a class of non-coding RNA with a transcription length over 200 nt and transcriptional regulation. lncRNA is extensively involved in physiological and pathological processes through epigenetic, transcription, and post-transcriptional regulation. Further, dysregulated lncRNA is closely related to the occurrence and development of human diseases, including CNS disorders. HOX Transcript antisense RNA (HOTAIR) is the first discovered lncRNA with trans-transcriptional regulation. Recent studies have shown that HOTAIR may participate in the regulation of the occurrence and development of CNS disorders. In addition, HOTAIR has the potential to become a new biomarker for the diagnosis and prognosis assessment of CNS disorders and even provide a new therapeutic target for CNS disorders. Here, we reviewed the research results of HOTAIR in CNS disorders to provide new insights into the pathogenesis, diagnostic value, and therapeutic target potential of HOTAIR in human CNS disorders.

Roles of lncRNAs in NF-κB-Mediated Macrophage Inflammation and Their Implications in the Pathogenesis of Human Diseases

“…It is often overexpressed in cancer, contributing to tumor progression, metastasis, and poor prognosis by altering gene expression related to the cell cycle, apoptosis, and metastasis [ 154 , 155 ]. HOTAIR is also associated with central nervous system disorders, fibrosis, and inflammatory conditions, impacting cellular processes and immune responses [ 156 , 157 , 158 , 159 ]. It regulates glucose transporter isoform 1 (GLUT1) expression in human neuroblastoma cells and macrophages by stimulating NF-κB activity, suggesting a role in metabolic reprogramming in cancer [ 117 , 160 ].…”

The role and clinical relevance of long non-coding RNAs in glioma

“…Notably, homeobox transcript antisense intergenic RNA (HOTAIR) is a well-known lncRNA epigenetic gene regulator. It indirectly silences homeobox D Cluster (HOXD) genes by facilitating the recruitment of the polycomb repressive complex 2 (PRC2) to the HOXD gene cluster, thereby promoting complex trimethylation of chromatin, leading to the repression of HOXD gene expression [ [33] , [34] , [35] ]. LncRNA X-inactive specific transcript (XIST) has been shown to play a role in chromatin regulation by modifying DNA/RNA and histone status [ 36 ].…”

“…In animal models, inhibiting HOTAIR was shown to suppress the invasion and metastasis of glioblastoma polymorphic cells [ 67 ]. Knocking out HOTAIR in glioma cells hindered their biological development, and miR-326 is believed to play a role in regulating this process [ 35 ]. Another potential therapeutic target is the tumor suppressor gene TSLC1, which influences glioma occurrence and development by modulating methylation.…”

Crosstalk among N6-methyladenosine modification and RNAs in central nervous system injuries

“…LncRNAs regulate gene expression at the epigenetic, transcriptional, post-transcriptional and chromatin remodeling levels via interacting with the 3′ untranslated region (UTR) of mRNA ( Chen et al, 2021 ). LncRNAs also interact with other biomolecules including deoxyribonucleic acids (DNAs), RNAs and proteins through several mechanisms, including acting as inhibitory sponges for miRNAs, participating in chromatin remodeling and affecting protein stability ( Wang J. et al, 2022 ).…”