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.
Galectin-3 is a biomarker of heart disease. However, it remains unknown whether increase in galectin-3 levels is dependent on aetiology or disease-associated conditions and whether diseased heart releases galectin-3 into the circulation. We explored these questions in mouse models of heart disease and in patients with cardiomyopathy. All mouse models (dilated cardiomyopathy, DCM; fibrotic cardiomyopathy, ischemia-reperfusion, I/R; treatment with β-adrenergic agonist isoproterenol) showed multi-fold increases in cardiac galectin-3 expression and preserved renal function. In mice with fibrotic cardiomyopathy, I/R or isoproterenol treatment, plasma galectin-3 levels and density of cardiac inflammatory cells were elevated. These models also exhibited parallel changes in cardiac and plasma galectin-3 levels and presence of trans-cardiac galectin-3 gradient, indicating cardiac release of galectin-3. DCM mice showed no change in circulating galectin-3 levels nor trans-cardiac galectin-3 gradient or myocardial inflammatory infiltration despite a 50-fold increase in cardiac galectin-3 content. In patients with hypertrophic cardiomyopathy or DCM, plasma galectin-3 increased only in those with renal dysfunction and a trans-cardiac galectin-3 gradient was not present. Collectively, this study documents the aetiology-dependency and diverse mechanisms of increment in circulating galectin-3 levels. Our findings highlight cardiac inflammation and enhanced β-adrenoceptor activation in mediating elevated galectin-3 levels via cardiac release in the mechanism.
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