{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T09:14:25Z","timestamp":1788426865940,"version":"build-2803163510"},"reference-count":39,"publisher":"Portland Press Ltd.","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DST-SERB Power grant","award":["SPG\/2021\/004755"],"award-info":[{"award-number":["SPG\/2021\/004755"]}]},{"name":"DST-INSPIRE","award":["IF180919"],"award-info":[{"award-number":["IF180919"]}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,9,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u20132.4 kb transcript, and an alternative upstream promoter\/TSS (P2), which contributes to context-dependent transcription initiation. Second, we examine the long-distance enhancer\u2013promoter 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\u2019s regulation.<\/jats:p>","DOI":"10.1042\/bst20260099","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T08:26:46Z","timestamp":1788424006000},"page":"1211-1219","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Insights into the regulation of the HOTAIR proximal promoter"],"prefix":"10.1042","volume":"54","author":[{"given":"Aritra","family":"Gupta","sequence":"first","affiliation":[{"name":"1Biotechnology Research Innovation Council-National Institute of Biomedical Genomics (BRIC-NIBMG), Kalyani, India"},{"name":"2PhD Program, Regional Centre for Biotechnology, Faridabad, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8974-0707","authenticated-orcid":false,"given":"Kartiki\u00a0V.","family":"Desai","sequence":"additional","affiliation":[{"name":"1Biotechnology Research Innovation Council-National Institute of Biomedical Genomics (BRIC-NIBMG), Kalyani, India"},{"name":"3Regional Centre for Biotechnology, Faridabad, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"2026090304264380800_B1","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1016\/j.cell.2007.05.022","article-title":"Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs","volume":"129","author":"Rinn","year":"2007","journal-title":"Cell"},{"key":"2026090304264380800_B2","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1038\/nature08975","article-title":"Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis","volume":"464","author":"Gupta","year":"2010","journal-title":"Nature"},{"key":"2026090304264380800_B3","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1038\/nature08975","article-title":"Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis","volume":"464","author":"Gupta","year":"2010","journal-title":"Nature"},{"key":"2026090304264380800_B4","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1186\/s12935-024-03612-x","article-title":"HOTAIR in cancer: diagnostic, prognostic, and therapeutic perspectives","volume":"24","author":"Nazari","year":"2024","journal-title":"Cancer Cell Int."},{"key":"2026090304264380800_B5","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1016\/j.cell.2007.05.022","article-title":"Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs","volume":"129","author":"Rinn","year":"2007","journal-title":"Cell"},{"key":"2026090304264380800_B6","doi-asserted-by":"publisher","first-page":"3707","DOI":"10.1016\/j.jmb.2013.01.022","article-title":"Antisense transcript long noncoding RNA (lncRNA) HOTAIR is transcriptionally induced by estradiol","volume":"425","author":"Bhan","year":"2013","journal-title":"J. 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