Prohibitin 2 orchestrates transcription of long noncoding RNA and coding gene to accelerate tumorigenesis
The spatial co-presence of aberrant long non-coding RNAs (lncRNAs) and abnormal coding genes contribute to the development of the malignancy in various tumors. However, precise coordinated mechanisms underlying this co-presence phenomenon in tumorigenesis remains incompletely understood. Here, we for the first time showed that PHB2 coordinately crosslinked transcription of a novel oncogenic CANT1-New-Isoform 2 (CANT2) lncRNA and coding tumor-suppressor gene CCBE1 for accelerating tumorigenesis of melanoma. In melanoma cells, PHB2 initially accessed open chromatin sites of the promoter of CANT2 lncRNA and recruited MLL2, resulting in an augmented H3K4 trimethylation and activating the transcription of CANT2. Intriguingly, PHB2 further bound with activated CANT2 transcript for targeting interaction with the promoter of tumor-suppressor CCBE1, recruiting histone deacetylase HDAC1 to decrease H3K27 acetylation of CCBE1 promoter and inhibiting CCBE1 transcription for significantly promoting cell growth and metastasis in vitro and in vivo. Our study elucidated a novel PHB2-mediating mechanism that crosslinked aberrant transcription of lncRNA and coding gene, thereby providing an interesting “one stone two birds” model in tumorigenesis. Overall design: We first generated CANT2 lncRNA knockout stable A375 cell lines with CRISPR/Cas9. Then RNA-seq was conducted on RNAs extracted from these CANT2-KO and control A375 cells.