Roles of HOTAIR Long Non-coding RNA in Gliomas and Other CNS Disorders

Sep 21, 2026

Uploaded by Patrick

HOX transcript antisense intergenic RNA (HOTAIR) is a long non-coding RNA increasingly recognized as a molecular mediator of brain pathophysiology across multiple levels. It drives epigenetic regulation through chromatin modifiers, notably PRC2 (with EZH2) and LSD1, and was the first lncRNA shown to sponge specific microRNA species in a trans-acting manner. This review summarizes its multifaceted pathogenic roles in gliomas and brain cancers, including biomarker potential for glioma grade and prognosis, and also discusses mechanisms in neurodegeneration and injury contexts such as traumatic, hypoxic, and ischemic brain damage, along with neuropsychiatric disorders.

LanguageEnglish

CategoryResearch & Report

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Pages20

Reading Time50 min

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Cellular and Molecular Neurobiology (2024) 44:23 [https://doi.org/10.1007/s10571-024-01455-8](https://doi.org/10.1007/s10571-024-01455-8) Roles of HOTAIR Long Non‑coding RNA in Gliomas and Other CNS Disorders Faraz Ahmad1 · Ravi Sudesh2 · A. Toufeeq Ahmed1 · Shafiul Haque3,4,5 Received: 15 June 2023 / Accepted: 18 January 2024 / Published online: 16 February 2024 © The Author(s) 2024 Abstract HOX transcript antisense intergenic RNA (HOTAIR) is a long non-coding RNA (lncRNA) which is increasingly being perceived as a tremendous molecular mediator of brain pathophysiology at multiple levels. Epigenetic regulation of target gene expression carried out by HOTAIR is thorough modulation of chromatin modifiers; histone methyltransferase polycomb repressive complex 2 (PRC2) and histone demethylase lysine-specific demethylase 1 (LSD1) . Incidentally, HOTAIR was the first lncRNA shown to elicit sponging of specific microRNA (miRNA or miR) species in a trans-acting manner. It has been extensively studied in various cancers, including gliomas and is regarded as a prominent pro-tumorigenic and pro-oncogenic lncRNA. Indeed, the expression of HOTAIR may serve as glioma grade predictor and prognostic biomarker. The objective of this timely review is not only to outline the multifaceted pathogenic roles of HOTAIR in the development and pathophysiology of gliomas and brain cancers, but also to delineate the research findings implicating it as a critical regulator of overall brain pathophysiology. While the major focus is on neuro-oncology, wherein HOTAIR represents a particularly potent underlying pathogenic player and a suitable therapeutic target, mechanisms underlying the regulatory actions of HOTAIR in neurodegeneration, traumatic, hypoxic and ischemic brain injuries, and neuropsychiatric disorders are also presented. Graphical Abstract HOTAIR-mediated epigenetic DNA regulation and molecular sponging of target miRNAs. While the 5 ′ end of HOTAIR regulates the H3K27 trimethylation activity of the catalytic subunit enhancer of Zeste homolog 2 (EZH2) of the polycomb repressive complex 2 (PRC2), its 3′ end modulates the H3K4 demethylation activity of lysine-specific demethylase 1 (LSD1) . Extended author information available on the last page of the article HOTAIR also binds to and competitively inhibits the functions of target miRNAs, altering the expression of downstream genes. Keywords Brain cancer · Alzheimer’s disease · Parkinson’s disease · Sponging · Neuropsychiatric diseases · Traumatic brain injury Introduction Long non-coding RNAs (lncRNAs) are RNA species with sizes greater than 200 nucleotides that are not translated into polypeptides. LncRNAs are widely localized at multiple genomic regions; however, they elicit considerable versatility in their biogenesis, cell-and tissue-specific expression patterns, and pathophysiological functions (Bridges et al. 2021) . The latest version of Gencode 43 (2022) catalog reports 19,928 lncRNA genes which produce a whopping cumulative total of 58,023 transcripts. The multifaceted cellular functions of lncRNAs are due to their ability to interact with diverse categories of biomolecules, including DNA, mRNA, proteins, and even other non-coding RNAs (e.g. , microRNAs or miRNAs) (Herman et al. 2022) . One of the prominent mechanisms by which lncRNAs influence cellular functions is by affecting chromatin organization and remodeling, transcription mechanisms, and splicing and export of mRNA species. Interestingly, lncRNAs also regulate the cytoplasmic stability, localization, miRNA-targeting and translation of other RNAs by acting as “molecular sponges”(Borkiewicz et al. 2021). Further, lncRNA species have been reported to induce posttranslational modifications of proteinaceous components (Srinivas et al. 2023) . Cells of the central nervous system (CNS) with all their morpho-functional complexities are tremendous targets of lncRNA-mediated alterations in pathophysiological proc

FAQs

What is HOTAIR and why is it considered important in brain pathophysiology?

HOTAIR is a long non-coding RNA that mediates brain pathophysiology through multiple regulatory layers, especially epigenetic control of gene expression and microRNA-related mechanisms.

How does HOTAIR regulate gene expression epigenetically?

HOTAIR modulates chromatin modifiers: its 5′ region regulates PRC2/EZH2 activity for H3K27 trimethylation, while its 3′ region influences LSD1 activity for H3K4 demethylation, resulting in transcriptional repression of target genes.

What role does HOTAIR play regarding microRNAs and downstream genes?

HOTAIR can bind to and competitively inhibit specific microRNAs, altering the expression of downstream genes through a molecular sponging mechanism.

Sep 21, 2026

Uploaded by Patrick