N6-methyladenosine modified lncRNAs signature for stratification of biochemical recurrence in prostate cancer.
Yingke LiangWenjun YinZhouda CaiHongwei LuoQinwei LiuChuanfan ZhongJiahong ChenZhuoyuan LinYaqiang HuangZhenguo LiangJunhong DengWeide ZhongChao CaiJianming LuPublished in: Human genetics (2023)
Nonmutational epigenetic reprogramming is a crucial mechanism contributing to the pronounced heterogeneity of prostate cancer (PCa). Among these mechanisms, N6-methyladenosine (m6A)-modified long non-coding RNAs (lncRNAs) have emerged as key players. However, the precise roles of m6A-modified lncRNAs in PCa remain to be elucidated. In this study, methylated RNA immunoprecipitation sequencing (MeRIP-seq) was conducted on primary and metastatic PCa samples, leading to the identification of 21 lncRNAs exhibiting differential methylation and expression patterns. We further established a PCa prognostic signature, named m6A-modified lncRNA score (mLs), based on 9 differential methylated lncRNAs in 4 multicenter cohorts. The high mLs score cohort exhibited a tendency for earlier biochemical recurrence (BCR) compared to the low mLs score cohort. Remarkably, the predictive performance of the mLs score surpassed that of five previously reported lncRNA-based signatures. Functional enrichment analysis underscored a negative correlation between the mLs score and lipid metabolism. Additionally, through MeRIP-qPCR, we pinpointed a hub gene, MIR210HG, which was validated through in vitro and in vivo experiments. These findings collectively illuminate the landscape of m6A-methylated lncRNAs in PCa tissue via MeRIP-seq and harness this information to prognosticate PCa outcomes using the mLs score. Furthermore, our study validates, both experimentally and mechanistically, the facilitative role of MIR210HG in driving PCa progression.
Keyphrases
- long non coding rna
- prostate cancer
- poor prognosis
- network analysis
- single cell
- genome wide
- genome wide identification
- genome wide analysis
- long noncoding rna
- cell proliferation
- dna methylation
- rna seq
- squamous cell carcinoma
- small cell lung cancer
- acute lymphoblastic leukemia
- healthcare
- clinical trial
- adipose tissue
- gene expression
- type diabetes
- transcription factor
- free survival
- metabolic syndrome
- insulin resistance
- social media
- weight loss