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Review
. 2023 Apr 15;42(1):86.
doi: 10.1186/s13046-023-02657-6.

Understanding the roles and regulation patterns of circRNA on its host gene in tumorigenesis and tumor progression

Jianxia Wei  1   2   3 , Mengna Li  1   2   3 , Changning Xue  1   2   3 , Shipeng Chen  1   2   3 , Lemei Zheng  1   2   3 , Hongyu Deng  1   2 , Faqing Tang  1 , Guiyuan Li  1   2   3 , Wei Xiong  1   2   3 , Zhaoyang Zeng  1   2   3 , Ming Zhou  4   5   6
Affiliations
Review

Understanding the roles and regulation patterns of circRNA on its host gene in tumorigenesis and tumor progression

Jianxia Wei et al. J Exp Clin Cancer Res. .

Abstract

Circular RNAs (circRNAs) are a novel type of endogenous non-coding RNAs, which are covalently closed loop structures formed by precursor mRNAs (pre-mRNAs) through back-splicing. CircRNAs are abnormally expressed in many tumors, and play critical roles in a variety of tumors as oncogenes or tumor suppressor genes by sponging miRNAs, regulating alternative splicing and transcription, cis-regulating host genes, interacting with RNA binding proteins (RBPs) or encoding polypeptides. Among them, the regulation of circRNAs on their corresponding host genes is a critical way for circRNAs to exit their functions. Accumulating evidence suggests that circRNAs are able to regulate the expression of host genes at the transcriptional level, post-transcriptional level, translational level, post-translational level, or by encoding polypeptides. Therefore, this paper mainly summarized the roles and association of circRNAs and their corresponding host genes in tumorigenesis and tumor progression, generalized the circRNAs that function synergistically or antagonistically with their host genes, and elaborated the mechanisms of mutual regulation between circRNAs and their host genes. More importantly, this review provides specific references for revealing the potential application of circRNAs combined with their host genes in tumor diagnosis, treatment and prognosis.

Keywords: CircRNA; Host gene; Regulation; Tumor progression; Tumorigenesis.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
CircRNAs regulate their host genes expression at the transcriptional level. A CircRNAs can be classified into three subtypes: exonic circRNAs (ecircRNAs), intronic circRNAs (ciRNAs), and exon-intron circRNAs (EIciRNAs). Some ciRNAs and EIciRNAs can promote the transcriptional activity of their host genes by binding to RNA polymerase II (Pol II). B CircRNAs can function as protein decoys, scaffolds or recruiters to promote or inhibit their host genes expression. C Some circRNAs, such as circSMARCA5, can increase the cleavage efficiency of homologous exon-defective mRNA by forming R-loops, which in turn terminated transcription, and affect their host genes expression
Fig. 2
Fig. 2
CircRNAs regulate the post-transcriptional modification of their host genes. A CircRNAs act as competing endogenous RNAs (ceRNAs) to relieve the adsorption of miRNAs on host genes and indirectly regulate the expression of their host genes. B CircRNAs, such as circ_0004296, function as protein sponges or decoys to regulate host gene expression and participate in the change of tumor malignant phenotype through post-transcriptional regulation. C CircRNAs enhance the stability of the host gene mRNA or induce the instability of the mRNA by directly interacting with the host gene mRNA or binding to RNA-binding proteins
Fig. 3
Fig. 3
CircRNAs regulate the translation process of their host genes. A Some circRNAs, such as circYap, regulate the translation process of host genes by binding to translation initiation related proteins, increasing or decreasing protein synthesis. B Some circRNAs, such as circPABPN1, act as translation inhibitors or activators to regulate the binding of RNA-binding proteins to the mRNA of host genes, inhibit or promote the translation process of host genes, and affect the synthesis of proteins
Fig. 4
Fig. 4
CircRNAs regulate post-translational modification of their host genes. A Some circRNAs, such as circFoxo3, regulate the activity and degradation of host proteins by recruiting proteins to regulate the ubiquitination of host proteins. B CircRNAs, such as circ-MYBL2, regulate the activity and degradation of host proteins by directly interacting with them to regulate the phosphorylation of host proteins
Fig. 5
Fig. 5
CircRNAs regulate their host genes expression by encoding polypeptides. A Small peptides encoded by circRNAs regulate the expression of host genes at the post-transcriptional level, thus participating in the malignant phenotype of tumors. B Small peptides encoded by circRNAs regulate endocytosis and degradation, cholesterol modification, ubiquitination and deubiquitination of host proteins at the post-translational level to regulate the stability of host proteins
Fig. 6
Fig. 6
Regulatory network of circRNAs and their host genes. Schematic diagram of the molecular mechanism by which circRNAs regulate the expression of host genes and then participate in the tumorigenesis and development at transcriptional, post-transcriptional, translational, and post-translational levels
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