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Prohibitin 2 orchestrates long noncoding RNA and gene transcription to accelerate tumorigenesis.
- Source :
-
Nature communications [Nat Commun] 2024 Sep 27; Vol. 15 (1), pp. 8385. Date of Electronic Publication: 2024 Sep 27. - Publication Year :
- 2024
-
Abstract
- The spatial co-presence of aberrant long non-coding RNAs (lncRNAs) and abnormal coding genes contributes to malignancy development in various tumors. However, precise coordinated mechanisms underlying this phenomenon in tumorigenesis remains incompletely understood. Here, we show that Prohibitin 2 (PHB2) orchestrates the transcription of an oncogenic CASC15-New-Isoform 2 (CANT2) lncRNA and the coding tumor-suppressor gene CCBE1, thereby accelerating melanoma tumorigenesis. In melanoma cells, PHB2 initially accesses the open chromatin sites at the CANT2 promoter, recruiting MLL2 to augment H3K4 trimethylation and activate CANT2 transcription. Intriguingly, PHB2 further binds the activated CANT2 transcript, targeting the promoter of the tumor-suppressor gene CCBE1. This interaction recruits histone deacetylase HDAC1 to decrease H3K27 acetylation at the CCBE1 promoter and inhibit its transcription, significantly promoting tumor cell growth and metastasis both in vitro and in vivo. Our study elucidates a PHB2-mediated mechanism that orchestrates the aberrant transcription of lncRNAs and coding genes, providing an intriguing epigenetic regulatory model in tumorigenesis.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Animals
Cell Line, Tumor
Melanoma genetics
Melanoma pathology
Melanoma metabolism
Mice
Mice, Nude
Cell Proliferation genetics
Histone Deacetylase 1 metabolism
Histone Deacetylase 1 genetics
Histones metabolism
RNA, Long Noncoding genetics
RNA, Long Noncoding metabolism
Prohibitins
Repressor Proteins metabolism
Repressor Proteins genetics
Carcinogenesis genetics
Gene Expression Regulation, Neoplastic
Promoter Regions, Genetic genetics
Transcription, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 39333493
- Full Text :
- https://doi.org/10.1038/s41467-024-52425-z