In this study, researchers from Harbin Medical University performed RNA-Seq of 33 breast specimens, and the expression of linc00152 was validated by qPCR using 50 paired breast cancer tissues and adjacent normal tissues. This result combined with the expression of linc00152 in pan-cancer was revalidated by Gene Expression Omnibus and The Cancer Genome Atlas data. Next, the oncogenic roles of linc00152 in view of prognosis, chemoresistance, genomic and epigenetic regulation, including DNA methylation and histone modification, potential biological function enrichment, and basic molecular function in pan-cancer, were also evaluated in vitro and in vivo.
Linc00152 is upregulated in pan-cancer, especially in progressive cancer, and the high expression of linc00152 may lead to a worse prognosis and chemoresistance in pan-cancer patients. Amplification, DNA hypomethylation, promoter-like lncRNA characteristics and super-enhancer regulation are the drivers that lead to the upregulation of linc00152 in pan-cancer. Meanwhile, linc00152 was involved in cancer-related pathways, infection and immune response-associated pathways by enriched analysis using TCGA data. Finally, linc00152 was confirmed to promote the proliferation, migration and invasion in MDA-MB-231, SGC-7901 and 786-O. Moreover, RIP and RNA pull-down assays indicated that linc00152 can bind to EZH2 directly.
Linc00152 and promoter/super-enhancer regulation
(A) Linc00152 as a promoter-like lncRNA via analysis of the ratio of H3K4me3/H3K4me1>1.2 in transcription start site of 15 cancer cell lines in the ENCODE data, especially in SK-N-MC cells marked with red. (B) Linc00152 is regulated by super-enhancers in six cancer cell lines in the SEA database. (C & D) The distance of 50 to 500 kb to the target gene transcription start sites was observed in 59 super-enhancers. (E) SE50407, a super-enhancer that regulates the expression of linc00152, was bound by oncogenic transcription factors.
These results indicated that linc00152 acted as an oncogenic propellant from various perspectives, and it may be an effective therapy target in pan-cancer.