Circular RNAs regulate parental gene expression: A new direction for molecular oncology research

Abstract

CircRNAs have been the focus of research in recent years. They are differentially expressed in various human tumors and can regulate oncogenes and tumor suppressor genes expression through various mechanisms. The diversity, stability, evolutionary conservatism and cell- or tissue-specific expression patterns of circRNAs also endow them with important regulatory roles in promoting or inhibiting tumor cells malignant biological behaviors progression. More interestingly, emerging studies also found that circRNAs can regulate not only other genes expression, but also their parental gene expression and thus influence tumors development. Apart from some conventional features, circRNAs have a certain specificity in the regulation of parental gene expression, with a higher proportion affecting parental gene transcription and easier translation into protein to regulate parental gene expression. CircRNAs are generally thought to be unable to produce proteins and therefore the protein-coding ability exhibited by circRNAs in regulating parental gene expression is unique and indicates that the regulatory effects of parental gene expression by circRNAs are not only a competitive binding relationship, but also a more complex molecular relationship between circRNAs and parental gene, which deserves further study. This review summarizes the molecular mechanisms of circRNAs regulating parental gene expression and their biological roles in tumorigenesis and development, aiming to provide new ideas for the clinical application of circRNAs in tumor-targeted therapy.

Identification of Circular RNA Profiles in the Liver of Diet-Induced Obese Mice and Construction of the ceRNA Network

“…Prediction of the function of these DE circRNAs can be made with reference to their parental genes [ 39 ]. Previous studies have shown that an important role of circRNAs is to regulate the expression of their linear counterparts, which can be positive or negative [ 40 ]. For example, CircFECR1 can reduce the promoter methylation of its parental gene and improve its expression through epigenetic mechanisms [ 41 ].…”

Circular RNAs and the regulation of gene expression in diabetic nephropathy (Review)

“…CircRNAs can regulate gene expression by acting as sponges for miRNAs or proteins ( 38 , 39 ). Other functions include participating as scaffold and cellular translocators ( 38 ), as well as regulating the expression of their parental gene ( 42 ), the translation of other proteins ( 43 ) or their translation to proteins ( 44 ) ( Fig. 1E ).…”

“…CircRNAs regulate the transcription of their parental genes in several ways ( 42 ). One of the methods includes invading the RNA-binding sites in the parental gene, thus blocking the binding of its linear isoform to the corresponding DNA sequence ( 54 ).…”

Myc derived circRNA promotes triple-negative breast cancer progression via reprogramming fatty acid metabolism

“…CircRNA is generated from pre-mRNA reverse splicing, thus one gene locus can generate multiple circRNAs through variable reverse splicing via altering the selection of splicing sites [ 13 ]. Studies have shown that some circRNAs regulated their parental gene expression or functions, participating in human disease progression [ 14 ]. For instance, circFOXO3 was shown to protect against osteoarthritis by activating autophagy via targeting its parental gene FOXO3 [ 15 ]; circYAP inhibited oncogenic YAP translation by suppressing the assembly of the translation initiation machinery [ 16 ].…”