H3K27 acetylation activated long noncoding RNA RP11-162G10.5 promotes breast cancer progression via the YBX1/GLO1 axis

• Published in: Cellular oncology (Dordrecht) 2023-04, Vol.46 (2), p.375-390
• Main Authors: Xie, Ning, Zhang, Ruihua, Bi, Zhuofei, Ren, Wei, You, Kaiyun, Hu, Hai, Xu, Ying, Yao, Herui
• Format: Article
• Language: English
• Subjects: Acetylation; Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer Research; Carcinogenesis - genetics; Cell Line, Tumor; Cell proliferation; Cell Proliferation - genetics; Cell Transformation, Neoplastic - genetics; Chromatin; Female; Gene Expression Regulation, Neoplastic; Histones; Histones - chemistry; Histones - metabolism; Humans; Lactoylglutathione Lyase - genetics; Lactoylglutathione Lyase - metabolism; Non-coding RNA; Oncology; Original Article; Pathology; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Therapeutic targets; Tumorigenesis; Y-Box-Binding Protein 1 - genetics; Y-Box-Binding Protein 1 - metabolism
• ISSN: 2211-3428; 2211-3436
• DOI: 10.1007/s13402-022-00756-8

Purpose Long noncoding RNAs (lncRNAs) orchestrate critical roles in human tumorigenesis. However, the regulatory mechanism of lncRNAs in tissue-specific expressions in breast cancer (BC) remains poorly understood. This study aims to investigate lncRNA role and mechanisms in BC. Methods RNA sequencing was used to explore differentially expressed lncRNAs in BC and adjacent tissues. H3K27 acetylation (H3K27ac) chromatin immune-precipitation sequencing (ChIP-seq) data of BC cells from the GEO dataset (GSE85158) was retrieved to identify the H3K27ac activated lncRNAs that were involved in tumorigenesis. RP11-162G10.5 was selected as the target lncRNA for further functional and mechanism study. Results In this study, we identified a novel lncRNA RP11-162G10.5, whose overexpression was specifically driven by H3K27ac in luminal breast cancer. And increased RP11-162G10.5 in BC is correlated with poor patient outcomes. RP11-162G10.5 promotes tumor cell proliferation in vitro and in vivo. Mechanistically, RP11-162G10.5 recruits transcriptional factor YBX1 to the GLO1 promoter, consequently activating GLO1 transcription to modulate the progression of BC. Conclusions Our findings suggest that the histone modification-activated lncRNA contributes to the oncogenesis of BC. Also, our data reveal a role for RP11-162G10.5 in BC tumorigenesis and may supply a strategy for targeting the RP11-162G10.5 as a potential biomarker and a therapeutic target for breast cancer patients.