No abstract

Covalently closed single-stranded circular RNAs (circRNAs) consist of introns or exons and are widely present in eukaryotic cells. CircRNAs generally have low expression levels and relatively stable structures compared with messenger RNAs (mRNAs), most of which are located in the cytoplasm and often act in cell type and tissue-specific manners, indicating that they may serve as novel biomarkers. In recent years, circRNAs have gradually become a hotspot in the field of RNA and cancer research, but the functions of most circRNAs have not yet been discovered. Known circRNAs can affect the biogenesis of cancers in diverse ways, such as functioning as a microRNA (miRNA) sponges, combining with RNA binding proteins (RBPs), working as a transcription factor and translation of proteins. In this review, we summarize the characteristics and types of circRNAs, introduce the biogenesis of circRNAs, discuss the emerging functions and databases on circRNAs and present the current challenges of circRNAs studies.

Background: Dynamic N 6-methyladenosine (m 6 A) RNA modification generated and erased by N 6methyltransferases and demethylases regulates gene expression, alternative splicing and cell fate. Ocular melanoma, comprising uveal melanoma (UM) and conjunctival melanoma (CM), is the most common primary eye tumor in adults and the 2nd most common melanoma. However, the functional role of m 6 A modification in ocular melanoma remains unclear. Methods: m 6 A assays and survival analysis were used to explore decreased global m 6 A levels, indicating a late stage of ocular melanoma and a poor prognosis. Multiomic analysis of miCLIP-seq, RNA-seq and Labelfree MS data revealed that m 6 A RNA modification posttranscriptionally promoted HINT2 expression. RNA immunoprecipitation (RIP)-qPCR and dual luciferase assays revealed that HINT2 mRNA specifically interacted with YTHDF1. Furthermore, polysome profiling analysis indicated a greater amount of HINT2 mRNA in the translation pool in ocular melanoma cells with higher m 6 A methylation. Results: Here, we show that RNA methylation significantly inhibits the progression of UM and CM. Ocular melanoma samples showed decreased m 6 A levels, indicating a poor prognosis. Changes in global m 6 A modification were highly associated with tumor progression in vitro and in vivo. Mechanistically, YTHDF1 promoted the translation of methylated HINT2 mRNA, a tumor suppressor in ocular melanoma. Conclusions: Our work uncovers a critical function for m 6 A methylation in ocular melanoma and provides additional insight into the understanding of m 6 A modification.