Transcriptome-Wide Map of N6-Methyladenosine Methylome Profiling in Human Bladder Cancer.

Aolin Li,Qian Zhang,Congcong Cao,Lin Yao,Quan Zhang,Binglei Ma,Ying Gan

doi:10.3389/fonc.2021.717622

Abstract

N6-Methyladenosine (m6A) is the most widespread internal RNA modification in several species. In spite of latest advances in researching the biological roles of m6A, its function in the development and progression of bladder cancer remains unclear. In this study, we used MeRIPty -55-seq and RNA-seq methods to obtain a comprehensive transcriptome-wide m6A profiling and gene expression pattern in bladder cancer and paired normal adjacent tissues. Our findings showed that there were 2,331 hypomethylated and 3,819 hypermethylated mRNAs, 32 hypomethylated and 105 hypermethylated lncRNAs, and 15 hypomethylated and 238 hypermethylated circRNAs in bladder cancer tissues compared to adjacent normal tissues. Furthermore, m6A is most often harbored in the coding sequence (CDS), with some near the start and stop codons between two groups. Functional enrichment analysis revealed that differentially methylated mRNAs, lncRNAs, and circRNAs were mostly enriched in transcriptional misregulation in cancer and TNF signaling pathway. We also found that different m6A methylation levels of gene might regulate its expression. In summary, our results for the first time provide an m6A landscape of human bladder cancer, which expand the understanding of m6A modifications and uncover the regulation of mRNAs, lncRNAs, and circRNAs through m6A modification in bladder cancer.

Highlights

Bladder transitional cell carcinoma (TCC) is the most common urothelial tumor in urology departments in China
We found that most of methylated sequences within mRNA, lncRNA, and circRNA in adjacent normal and tumor tissues contained less than five m6A peaks, while few of them contained five or more sites (Figures 1D–F)
We found that a low expression of METTL14, sphingomyelin phosphodiesterase 4 (SMPD4), and SGK2, but a high expression of ALKBH5, LINC00482, and HIPK3, showed a tendency to associate with worse overall survival in bladder cancer patients (Figures 6C–H)

Summary

Introduction

Bladder transitional cell carcinoma (TCC) is the most common urothelial tumor in urology departments in China. The vast majority originated from epithelial tissue, and TCC accounts for more than 90% [1,2,3]. The diagnosis of bladder transitional cell carcinoma mainly relies on invasive cystoscopy and pathological biopsy. The biggest difficulty in the treatment of bladder cancer is its easy recurrence. Detection of bladder cancer can improve the chances of bladder preservation and overall survival. After bladder-sparing tumor resection, even with regular infusion of chemotherapy into the bladder, there is still a 10% to 40% recurrence rate, and some of them

Methods

Results

Conclusion