CircPVT1: a pivotal circular node intersecting Long Non-Coding-PVT1 and c-MYC oncogenic signals

Abstract

The role of circular RNAs in oncogenesis has begun to be widely studied in recent years, due to the significant impact that these molecules have in disease pathogenesis, as well as their potential for the future of innovative therapies. Moreover, due to their characteristically circular shape, circular RNAs are very resistant molecules to RNA degradation whose levels are easily assessed in body fluids. Accordingly, they represent an opportunity for the discovery of new diagnostic and prognostic markers in a wide range of diseases. Among circular RNAs, circPVT1 is a rather peculiar one that originates from the circularization of the exon 2 of the PVT1 gene that encodes a pro-tumorigenic long non-coding RNA named lncPVT1. There are a few examples of circular RNAs that derive from a locus producing another non-coding RNA. Despite their apparent transcriptional independence, which occurs using two different promoters, a possible synergistic effect in tumorigenesis cannot be excluded considering that both have been reported to correlate with the oncogenic phenotype. This complex mechanism of regulation appears to also be controlled by c-MYC. Indeed, the PVT1 locus is located only 53 Kb downstream c-MYC gene, a well-known oncogene that regulates the expression levels of about 15% of all genes. Here, we review circPVT1 origin and biogenesis highlighting the most important mechanisms through which it plays a fundamental role in oncogenesis, such as the well-known sponge activity on microRNAs, as well as its paradigmatic interactome link with lncPVT1 and c-MYC expression.

Advances in the Study of circRNAs in Hematological Malignancies

“…hsa-circRNA-101237 expression in the bone marrow is significantly upregulated in patients with MM, in MM cell lines, and in BTZ-resistant MM cells, especially those with recurrent/refractory disease ( 102 ). hsa-circRNA-101237 expression was found to significantly increase in patients who had MM with t ( 4 , 14 ), t ( 14 , 16 ), 13q14 deletion, P53 deletion, and 1q21 amplification; the hsa-circRNA-101237 expression was related to the prognosis, OS, and progression free survival (PFS) of patients with MM ( 102 ). circ_0007841 was overexpressed in MM cell lines and patients with MM and induced the activation of the PI3K/AKT signaling pathway via the miR-338-3p/bromodomain containing 4(BRD4) axis ( 64 ).…”

“…The gene on chromosome 8q24.21 is named human plasmacytoma variant translocation 1 ( PVT1 ), which is located 54 kb far downstream of MYC. circPVT1 is generated by cyclization of exon 2 of PVT1 ( 16 , 76 ). High circPVT1 expression in ALL leads to the inhibition of c-MYC expression, in turn inhibited the apoptosis of ALL cells and promotion of cell proliferation ( 50 ).…”

“…Subsequently, circRNAs were found in hepatitis D virus, which was the first instance that circRNAs were detected in an animal virus ( 15 ). Earlier, studies were not conducted on circRNAs because they were considered as minor products of RNA missplicing ( 16 , 17 ). With the development of analytical techniques such as RNA sequencing and informatics tools, circRNAs have been detected in various eukaryotes (e.g., mice), as well as in human plasma and saliva ( 8 , 10 , 18 – 20 ).…”

Li–Fraumeni Syndrome: Mutation of TP53 Is a Biomarker of Hereditary Predisposition to Tumor: New Insights and Advances in the Treatment

“…Wt and mut p53 expression have been correlated with the expression of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) whose main function is to refine the regulation of a plethora of genes correlated with cell proliferation and metabolism [ 78 , 79 , 80 , 81 , 82 ]. From the point of view of LFS, a common single nucleotide polymorphism (SNP) within miR-605 (rs2043556) was associated with gastrointestinal cancer risk and one of its most important reported functions is to target MDM2 mRNA, one of the major regulators of protein stability of both wt and mut p53 [ 83 , 84 ].…”

Circulating circular RNA hsa_circ_0023179 acts as a diagnostic biomarker for non-small-cell lung cancer detection

“…Eukaryotic circular RNAs were found in the early 1990s and were considered results of error splicing or splicing intermediates (Cocquerelle, Mascrez, Hétuin, & Bailleul, 1993). Meanwhile, traditional RNA detection methods using electrophoresis or size mobility transfer tests could not detect circRNA molecules (Palcau et al, 2022). As a result, the study of circRNA has not been widely carried out until recent years.…”