Department of Biotechnology, School of Bio Sciences (SBST), Vellore Institute of Technology (VIT), Vellore, 632014, India.
Department of Biomedical Sciences, School of Bio Sciences (SBST), Vellore Institute of Technology (VIT), Vellore, 632014, India.
Cell Mol Neurobiol. 2024 Feb 16;44(1):23. doi: 10.1007/s10571-024-01455-8.
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.
HOX 转录反义基因间 RNA（HOTAIR）是一种长链非编码 RNA（lncRNA），它被越来越多地认为是多种水平脑病理生理学的巨大分子介质。HOTAIR 对靶基因表达的表观遗传调控是通过染色质修饰剂的全面调节来实现的；组蛋白甲基转移酶多梳抑制复合物 2（PRC2）和组蛋白去甲基酶赖氨酸特异性去甲基酶 1（LSD1）。顺便说一句，HOTAIR 是第一个被证明以反式作用方式引发特定 microRNA（miRNA 或 miR）物种海绵化的 lncRNA。它已在各种癌症中得到广泛研究，包括神经胶质瘤，并被认为是一种突出的促肿瘤发生和致癌 lncRNA。事实上，HOTAIR 的表达可以作为神经胶质瘤分级预测因子和预后生物标志物。本次及时审查的目的不仅是概述 HOTAIR 在神经胶质瘤和脑癌的发生和病理生理学中的多方面致病作用，还在于阐述将其作为整体脑病理生理学关键调节因子的研究结果。虽然主要重点是神经肿瘤学，其中 HOTAIR 是一个特别强大的潜在致病因素和一个合适的治疗靶点，但在神经退行性变、创伤性、缺氧和缺血性脑损伤以及神经精神疾病中，HOTAIR 的调节作用的机制也被提出。
