Comprehensive Characterization of Circular RNAs in Neuroblastoma Cell Lines

Abstract

Neuroblastoma (NB) is a rare type of cancer but frequently occurred in children. However, it is still unclear whether circular RNAs (circRNAs) play key roles in NB tumorigenesis or progression. In this study, we identified 39,022 circRNAs across the 39 neuroblastoma and 2 normal cell lines. With the gene and circRNA expression data, we classified the NB cell lines, identified and characterized the functional circRNAs in the 3 NB classes. Specifically, 29 circRNAs were found to be dysregulated in the NB classes. Notably, 7 circRNAs located within MYCN-amplified regions were upregulated in cell lines with the high activities of MYC targets and MYCN amplification, and were highly correlated with expression of their parental gene, NBAS. Subsequently, we constructed ceRNA networks for the functional circRNAs. Specifically, hsa_circ_0005379 was identified as a critical regulator in the ceRNA networks because of targeting 13 genes, which formed a complex competing endogenous RNA (ceRNA) network. Moreover, hsa_circ_0002343, which was connected with few genes, might regulate the PI3K/Akt/mTOR signaling via RAC1. Furthermore, 3 genes, including NOTCH2, SERPINH1, and LAMC1, involved in epithelial mesenchymal transition (EMT) were observed to connect with hsa_circ_0001361, suggesting that this circRNA was closely associated with EMT. Consequently, 7 genes, such as DAD1, PPIA, NOTCH2, PGK1, BUB1, EIF2S1, and TCF7L2, were found to be closely associated with both event-free survival (EFS) and overall survival (OS). In conclusion, the present study identified functional circRNAs and predicted their functionality in neuroblastoma cell lines, which not only improved the understanding of circRNAs in neuroblastoma, but also provided the evidences for the related researchers.

A Critical Role of Peptidylprolyl Isomerase A Pseudogene 22/microRNA-197-3p/Peptidylprolyl Isomerase A Axis in Hepatocellular Carcinoma

“…MYC has been proved to have a board range of functions, including but not limited to cell biology, cell cycle, apoptosis, the molecular basis of cancer ( Meyer and Penn, 2008 ). Meanwhile, MYC has been found involved in the tumorigenesis or progression in neuroblastoma and genotype-C-HBV-related HCC via regulating the PPIA expression ( Iizuka et al, 2006 ; Zhang et al, 2020b ). In this regard, PPIA may be regulated by MYC to some extent in HCC, apart from PPIAP22.…”

hsa_circ_0001955 Promotes Colorectal Cancer Progression by Regulating miR-583/FGF21 Axis

“…CircRNAs adsorb miRNAs via functioning as miRNA molecular sponges [ 21 , 22 ], thus regulating gene expression, and are widely involved in life activities and tumor progression [ 23 – 25 ]. Increasing numbers of studies also revealed the sponging of circRNAs with miRNAs regulates CRC progression.…”

In Vitro Assessment of the Role of p53 on Chemotherapy Treatments in Neuroblastoma Cell Lines

“…Circular RNAs might also be considered as regulators of translation [53][54][55][56]. CircRNA-TBC1D4, circRNA-NAALAD2, and circRNA-TGFBR3 may be tumor suppressor genes in neuroblastoma.…”