Circular RNAs: clinical relevance in cancer

Xu, Zhijie; Yan, Yuanliang; Zeng, Shuangshuang; Dai, Shuang; Chen, Xi; Wei, Jie; Gong, Zhicheng

doi:10.18632/oncotarget.22846

Cited by 52 publications

(36 citation statements)

References 119 publications

(131 reference statements)

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“…Circular RNA (circRNA) is a type of RNA capable of forming a covalently closed continuous loop [ 1 , 2 ]. CircRNAs are mostly non-translated, can occur in any genomic region including gene-bearing regions and intergenic regions, and range in length from few hundred to thousands of nucleotides [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Regarding the function of circRNAs, it can be briefly categorized into several aspects, including downregulating miRNA by absorbing or sponging them, regulation their parental genes transcription, serve as a biomarker for age, cancer, etc. Among all of the functions listed above, miRNA sponging is the one of the functions discovered by Memczak et al at the first time, revealing that circRNA could act as a sponge to bind and sequester miRNA in a sequence-specific manner [ 2 ]. Since the well-accepted function of miRNA in cancer, many attentions have been drawn concerning the roles of circRNAs in initiation and progression of cancer [ 1 – 3 ].…”

Section: Introductionmentioning

confidence: 99%

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Circ-ZEB1.33 promotes the proliferation of human HCC by sponging miR-200a-3p and upregulating CDK6

Gong

Mao²,

et al. 2018

Cancer Cell Int

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BackgroundAccumulating data indicated that circRNA plays important roles in regulating many biological processes of the tumor, the present study is designated for exploring roles of the circ-ZEB1.33-miR-200a-3p-CDK6 regulating axis in human hepatocellular carcinoma (HCC).MethodsThe regulation axis as predicted by using online tool circNet, the expression and correlation of circ-ZEB1.33-miR-200a-3p-CDK6 was verified in human HCC. The diagnostic value of both tumor and serum circ-ZEB1.33 was estimated by using clinical samples. The roles of circ-ZEB1.33-miR-200a-3p-CDK6 in regulating cell cycle were explored by using in vitro studies.ResultsOverexpression of circ-ZEB1.33 and CDK6, downregulation of miR-200a-3p were detected in human HCC tissues, negative correlation between circ-ZEB1.33 and miR-200a-3p, positive correlation between circ-ZEB1.33 and CDK6 were confirmed in human HCC tissues. Tissue and serum circ-ZEB1.33 were related to different TMN stages and prognosis in HCC patients. RNA pull-down assay implied that circ-ZEB1.33 could decrease miR-200a-3p by sponging miR-200a-3p, and the luciferase reporter assay indicated that miR-200a-3p could downregulate CDK6 transcription by targeting its 3′UTR. The in vitro assays indicated that circ-ZEB1.33 could promote the proliferation of HCC cells by increasing the percentage of S phase regulated by CDK6/Rb.ConclusionProliferation promotion roles of the circ-ZEB1.33-miR-200a-3p-CDK6 regulating axis are existed and verified in human HCC, both tumor and serum circ-ZEB1.33 can serve as an indicator for the prognosis of HCC patients.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0602-3) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Circ-ZEB1.33 promotes the proliferation of human HCC by sponging miR-200a-3p and upregulating CDK6

Gong

Mao²,

et al. 2018

Cancer Cell Int

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“…More confident evidence has verified that circRNAs function crucially in cancer development and progression . Nevertheless, their functions in BC remain largely unclear.…”

Section: Discussionmentioning

confidence: 99%

Silencing circular RNA VANGL1 inhibits progression of bladder cancer by regulating miR‐1184/IGFBP2 axis

et al. 2019

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Circular RNA VANGL1 (circVANGL1) is generated from two exons of the Van Gogh‐like 1 (VANGL1) gene and serves as a tumor promoter by sponging certain microRNAs (miRNAs). However, the role of circVANGL1 in bladder cancer (BC) is still unclear. So, in order to investigate the role of circVANGL1 in BC, quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) was employed to evaluate the circVANGL1 expression in tumor tissues from BC patients and in BC cell lines. Small interfering RNA against circVANGL1 was constructed and stably transfected into human bladder epithelium immortalized cells (SV‐HUC). Cell invasion and migration were detected in Transwell chambers, cell proliferation was determined by CCK8 assays, and tumorigenesis in nude mice was examined to assess the effect of circVANGL1 in BC. Subcellular localization of circVANGL1 was confirmed by fluorescence in situ hybridization. The interactive relationships among circVANGL1, miRNA, and relative proteins were confirmed by luciferase reporter assays. The results showed that circVANGL1 was upregulated in both BC tissues and cell lines. Silencing the expression of circVANGL1 suppressed cell invasion, migration, and proliferation during in vitro experiments. Mechanistically, we demonstrated that circVANGL1 upregulated the expression of miR‐1184 target gene insulin‐like growth factor‐binding protein 2 (IGFBP2) by sponging miR‐1184, which promoted the aggressive biological behaviors of BC. Taken together, our results indicate that circVANGL1 acts as a tumor promoter through the novel circVANGL1/miR‐1184/IGFBP2 axis. Hopefully, our study will provide new ideas for the clinical treatment of BC.

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“…Indeed, multiple MREs are present in ceRNAs and enable direct interactions with miRNAs, thereby preventing binding of these miRNAs to their respective target mRNAs (Figure 1d). The role of ceRNAs in various cellular processes (e.g., cell cycle, apoptosis) is well established, and alteration of their expression contributes to the onset of various pathologies [76][77][78]. One representative and well-studied example of such regulation is provided by the phosphatase and tensin homologue, pseudogene 1 (PTENP1), which can sponge various miRNAs (e.g., miR-21, miR-106b and miR-93) targeting the 3 UTR of the tumor suppressor gene phosphatase and tensin homologue (PTEN) [79,80].…”

Section: Mirna-cerna Interactionsmentioning

confidence: 99%

Deciphering miRNAs’ Action through miRNA Editing

Sousa

Gjorgjieva

Dolicka

et al. 2019

IJMS

635

343

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MicroRNAs (miRNAs) are small non-coding RNAs with the capability of modulating gene expression at the post-transcriptional level either by inhibiting messenger RNA (mRNA) translation or by promoting mRNA degradation. The outcome of a myriad of physiological processes and pathologies, including cancer, cardiovascular and metabolic diseases, relies highly on miRNAs. However, deciphering the precise roles of specific miRNAs in these pathophysiological contexts is challenging due to the high levels of complexity of their actions. Indeed, regulation of mRNA expression by miRNAs is frequently cell/organ specific; highly dependent on the stress and metabolic status of the organism; and often poorly correlated with miRNA expression levels. Such biological features of miRNAs suggest that various regulatory mechanisms control not only their expression, but also their activity and/or bioavailability. Several mechanisms have been described to modulate miRNA action, including genetic polymorphisms, methylation of miRNA promoters, asymmetric miRNA strand selection, interactions with RNA-binding proteins (RBPs) or other coding/non-coding RNAs. Moreover, nucleotide modifications (A-to-I or C-to-U) within the miRNA sequences at different stages of their maturation are also critical for their functionality. This regulatory mechanism called "RNA editing" involves specific enzymes of the adenosine/cytidine deaminase family, which trigger single nucleotide changes in primary miRNAs. These nucleotide modifications greatly influence a miRNA's stability, maturation and activity by changing its specificity towards target mRNAs. Understanding how editing events impact miRNA's ability to regulate stress responses in cells and organs, or the development of specific pathologies, e.g., metabolic diseases or cancer, should not only deepen our knowledge of molecular mechanisms underlying complex diseases, but can also facilitate the design of new therapeutic approaches based on miRNA targeting. Herein, we will discuss the current knowledge on miRNA editing and how this mechanism regulates miRNA biogenesis and activity.

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Circular RNAs: clinical relevance in cancer

Cited by 52 publications

References 119 publications

Circ-ZEB1.33 promotes the proliferation of human HCC by sponging miR-200a-3p and upregulating CDK6

Circ-ZEB1.33 promotes the proliferation of human HCC by sponging miR-200a-3p and upregulating CDK6

Silencing circular RNA VANGL1 inhibits progression of bladder cancer by regulating miR‐1184/IGFBP2 axis

Deciphering miRNAs’ Action through miRNA Editing

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