Insights into the regulation of the HOTAIR proximal promoter.

Aritra Gupta; Kartiki V Desai

doi:10.1042/bst20260099

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Insights into the regulation of the HOTAIR proximal promoter.

Aritra Gupta·Kartiki V Desai

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Abstract

HOTAIR (HOX transcript antisense RNA) is a HOXC-cluster long intervening non-coding RNA (lincRNA) whose cancer relevance is tightly coupled to how its transcription is wired into hormone, hypoxia, inflammatory, and developmental signaling. HOTAIR is known to associate with cancer cell proliferation, motility, tumor invasion, and metastasis. The present mini-review focuses on the regulatory architecture and mechanistic complexity of HOTAIR transcriptional regulation, with emphasis on three organizing principles. First, we consider the impact of promoter choice between a canonical proximal promoter (P1), which supports the 2.2-2.4 kb transcript, and an alternative upstream promoter/TSS (P2), which contributes to context-dependent transcription initiation. Second, we examine the long-distance enhancer-promoter communication between HOTAIR distal enhancer and P1/P2. Third, we summarize the recent epigenetic and epi-transcriptomic mechanisms involved in HOTAIR transcript initiation and elongation. A combination of these events determines isoform-specific transcription to govern cell-type-, context-, and cancer specific modulation of HOTAIR expression that promotes tumor formation and cancer progression. Finally, the review proposes how large-scale RNA datasets, long-read sequencing, and isoform-specific studies can refine our understanding of this versatile lincRNA's regulation.

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Humans Promoter Regions, Genetic RNA, Long Noncoding Neoplasms Gene Expression Regulation, Neoplastic Epigenesis, Genetic Animals Transcription, Genetic Enhancer Elements, Genetic Cancer eukaryotic gene expression long intervening non-coding RNA Journal Article Review

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Aritra Gupta, Kartiki V Desai. 2026-09-23. Insights into the regulation of the HOTAIR proximal promoter.. https://doi.org/10.1042/bst20260099

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Journal Article; Review resource Animals subject Cancer subject Epigenesis, Genetic subject Gene Expression Regulation, Neoplastic subject Humans subject Journal Article subject Neoplasms subject Promoter Regions, Genetic subject

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