N6-methyladenosine (m6A) is the most prevalent internal RNA modification, especially within eukaryotic messenger RNAs (mRNAs). m6A modifications of RNA regulate splicing, translocation, stability, and translation into proteins. m6A modifications are catalyzed by RNA methyltransferases, such as METTL3, METTL14, and WTAP (writers); the modifications are removed by the demethylases fat mass and obesity-associated protein (FTO) and ALKBH5 (ALKB homolog 5) (erasers); and the modifications are recognized by m6A-binding proteins, such as YTHDF domain-containing proteins and IGF2BPs (readers). Abnormal changes in the m6A levels of these genes are closely related to tumor occurrence and development. In this paper, we review the role of m6A in human cancer and summarize its prospective applications in cancer.

Circular RNAs (circRNAs) are novel members of the noncoding RNA family. Their characteristic covalent closed-loop structure endows circRNAs that are much more stable than the corresponding linear transcript. circRNAs are ubiquitous in eukaryotic cells, and their functions are diverse and include adsorbing microRNAs (miRNAs; acting as miRNA sponges), regulating transcription, interacting with RNA-binding proteins, and translating and deriving pseudogenes. Moreover, circRNAs are associated with the occurrence and progression of a variety of cancers, acting as new biomarkers for early diagnosis to evaluate curative effects and patient prognosis. Here, this paper briefly describes the characteristics and functions of circRNAs, and it further concludes the relationship between circRNAs and human cancer.

Emerging evidences have suggested the vital roles of circular RNA (circRNA) in the human cancers. However, the underlying biological functions and biogenesis of circRNA in the oral squamous cell carcinoma (OSCC) is still ambiguous. Here, we investigate the oncogenic roles and biogenesis of the novel identified circRNA, circUHRF1 (hsa_circ_0002185), in the OSCC tumorigenesis. Results showed that circUHRF1 was markedly upregulated in the OSCC cells and tissue, besides, the overexpression was closely correlated with the poor prognosis of OSCC patients. Functionally, circUHRF1 promoted the proliferation, migration, invasion, and epithelial mesenchymal transformation (EMT) in vitro and the tumor growth in vivo. Mechanically, circUHRF1 acted as the sponge of miR-526b-5p, thereby positively regulating c-Myc. Transcription factor c-Myc could accelerate the transcription of TGF-β1 and ESRP1. Moreover, splicing factor ESRP1 promoted the circularization and biogenesis of circUHRF1 by targeting the flanking introns, forming the circUHRF1/miR-526b-5p/c-Myc/ TGF-β1/ESRP1 feedback loop. In conclusion, our research identified the oncogenic roles of circUHRF1 in the OSCC tumorigenesis and EMT via circUHRF1/miR-526b-5p/c-Myc/TGF-β1/ESRP1 feedback loop, shedding light on the pathogenic mechanism of circUHRF1 for OSCC and providing the potential therapeutic target.

N 6 -Methyladenosine (m 6 A) is the most common internal modification of eukaryotic messenger RNA (mRNA) that occurred on the N 6 nitrogen of adenosine. However, the roles of m 6 A in oral squamous cell carcinoma (OSCC) are still elusive. Here, we investigate the function and mechanism of methyltransferase-like 3 (METTL3) in OSCC tumorigenesis. Clinically, METTL3 was significantly upregulated in tissue samples and correlated with the poor prognosis of OSCC patients. Functionally, loss and gain studies illustrated that METTL3 promoted the proliferation, invasion, and migration of OSCC cells in vitro, and METTL3 knockdown inhibited tumor growth in vivo. Mechanistically, methylated RNA immunoprecipitation sequencing (MeRIP-seq) illustrated that METTL3 targeted the 3 0 UTR (near to stop codon) of the c-Myc transcript to install the m 6 A modification, thereby enhancing its stability. Furthermore, results revealed that YTH N 6 -methyladenosine RNA binding protein 1 (YTH domain family, member 1 [YTHDF1]) mediated the m 6 Aincreased stability of c-Myc mRNA catalyzed by METTL3. In conclusion, our findings herein identify that METTL3 accelerates the c-Myc stability via YTHDF1-mediated m 6 A modification, thereby giving rise to OSCC tumorigenesis.

No abstract