Circular <scp>RNA</scp>s in hepatocellular carcinoma: Functions and implications

Fu, Liyun; Jiang, Zhibing; Li, Tianwen; Hu, Yaoren; Guo, Junming

doi:10.1002/cam4.1574

Cited by 109 publications

(94 citation statements)

References 78 publications

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“…CircRNAs may function as ceRNAs to retain endogenous RNA and regulate the expression of related genes . For example, circLARP4 from the LARP4 pre‐mRNA inhibits the occurrence and progression of GC by affecting the expression of cavernous miR‐424 and increasing the expression of LATS1 …”

Section: Biological Functions Of Circrnasmentioning

confidence: 99%

“…(ii) Specificity: circRNAs are expressed in a tissue‐specific and developmental stage‐specific way. In particular, many studies have shown that circRNAs are distinctively expressed between cancerous and noncancerous tissues . (iii) Universality: circRNAs are considered to be the most widely distributed molecules in human cells.…”

Section: Tumor‐suppressive Circrnas May Be Used As Tumor Biomarkersmentioning

confidence: 99%

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Tumor‐suppressive circular RNAs: Mechanisms underlying their suppression of tumor occurrence and use as therapeutic targets

et al. 2019

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internal ribosome entry site; LARP4, La-related protein 4; LATS1, large tumor suppressor kinase 1; lncRNAs, long noncoding RNAs; MIBC, muscle invasive bladder cancer; miRNA, microRNA; ncRNAs, noncoding RNAs; NF1, neurofibromin 1; Notch1, notch homolog 1; NSCLC, non-small cell lung cancer; OS, overall survival; PCK1, phosphoenolpyruvate carboxykinase 1; PDAC, pancreatic ductal adenocarcinoma; RBP, RNA-binding protein; RCAN1, regulation of Down syndrome critical region gene 1; sncRNAs, short noncoding RNAs; TIMP3, metalloproteinase inhibitor 3; USP28, ubiquitin-specific peptidase 28; YBX1, Y box binding protein 1. AbstractCircular RNAs (circRNAs) have a covalently closed circular conformation and are structurally stable. Those circRNAs with tumor-suppressive properties play an important role in tumorigenesis and metastasis and thus may be used as therapeutic targets of cancers. Herein, we review the current understanding of the classification of circRNAs and summarize the functions and mechanisms of circRNAs that have tumor-suppressive roles in various cancers, including liver cancer (circARSP91, circ-ADAMTS13, circADAMTS14, circMTO1, hsa_circ_0079299, and circC3P1), bladder cancer (circFNDC3B, circITCH, circHIPK3, circRNA-3, cdrlas, and circLPAR1), gastric cancer (circLARP4, circYAP1, hsa_cric_0000096, hsa_circ_0000993, and circPSMC3), breast cancer (circ_000911, hsa_circ_0072309, and circASS1), lung cancer (hsa_ circ_0000977, circPTK2, circ_0001649, hsa_circ_100395, and circ_0006916), glioma (circ_0001946, circSHPRH, and circFBXW7), and colorectal cancer (circITGA7 and hsa_circ_0014717). Thanks to their structural stability, these tumor-suppressive cir-cRNAs may be used as potential and potent therapeutic targets. Moreover, we propose a new method for the classification of circRNAs. Based on whether they can be translated, circRNAs can be divided into noncoding circRNAs and coding circRNAs. K E Y W O R D Sbiogenesis, cancer, circular RNA, mechanism, therapeutic target | INTRODUC TI ONThose RNAs that do not encode proteins are called ncRNAs. 1 Regulatory ncRNAs are divided into lncRNAs and sncRNAs. LncRNAs can be linear or circular. 2 Circular RNAs were first discovered in 1976. 3 Since then, a variety of circRNAs have been discovered. 4,5 CircRNAs are more resistant to exonuclease and are more stable than other lncRNAs. 3,6 They exist in exosomes and plasma. 6,7 Li et al identified more than 1000 circRNAs in human serum exosomes. 6 Li et al found 343 differentially How to cite this article:

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Section: Biological Functions Of Circrnasmentioning

confidence: 99%

Section: Tumor‐suppressive Circrnas May Be Used As Tumor Biomarkersmentioning

confidence: 99%

Tumor‐suppressive circular RNAs: Mechanisms underlying their suppression of tumor occurrence and use as therapeutic targets

et al. 2019

Self Cite

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“…Then, we demonstrated that circARNT2 was upregulated in HCC tissues and associated with cisplatin resistance in HCC. To further validate whether circARNT2 functionally required for cisplatin resistance, we performed loss-of-function studies by CircRNAs may act as transcription regulators or as sponges for small RNA regulators, which compete for microRNA (miRNA) activity in the process of regulating cell proliferation 22 . Most circRNAs have miRNAbinding sites that can be used as miRNA sponges to inhibit the regulation of miRNAs on downstream target genes by a large number of miRNAs in cancers 23 .…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circARNT2 Suppressed The Sensitivity of Hepatocellular Carcinoma Cells to Cisplatin by Targeting The miR-155-5p/PDK1 Axis

Weng

Cao

Chen

et al. 2020

Preprint

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Abstract Background: Circular RNA (circRNA) is a novel subclass of noncoding-RNA molecules that participate in development and progression of a variety of human diseases via sponging microRNAs (miRNAs). Until now, the contributions of circRNAs in chemoresistance of hepatocellular carcinoma (HCC) remain largely unknown.Methods: In the present study, we aimed to investigate the role of circRNA in cisplatin resistance of HCC. We investigated the expression of circRNAs in 5 paired cisplatin-sensitive and cisplatin-resistant HCC tissues by microarray analysis. The qRT-PCR analysis was to investigate the expression pattern of circARNT2 in HCC patient tissues and cell lines. Then, the effects of circARNT2 on cisplatin resistance, cell proliferation, and apoptosis were assessed in HCC in vitro and in vivo.Results: CircARNT2 was significantly upregulated in HCC tissues and cell lines. Overexpression of circARNT2 in HCC was significantly correlated with aggressive characteristics and served as an independent risk factor for overall survival in patients with HCC. In vitro experiments showed that knockdown of circARNT2 inhibited cell proliferation and enhances the cisplatin sensitivity of HCC cells. Furthermore, circARNT2 facilitates HCC progression in vivo. We demonstrated that circARNT2 acts as a sponge for miR-155-5p and verified that PDK1 is a novel target of miR-155-5p.Conclusion: In summary, our study demonstrated that circARNT2 modulates cisplatin resistance through miR-155-5p/PDK1 pathway. Our findings indicated that circARNT2 may serve as a promising therapeutic target for overcoming cisplatin resistance for HCC.

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“…137 Overall, circRNAs played key roles in tumorigenesis and development, epigenetic regulation, drug resistance, and could be considered as immune-associated biomarker and therapeutic target in HCC. [138][139][140][141][142][143][144] Regardless, more in-depth study of circRNA biofunctions in HCC is greatly desired.…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

<p>Biological Roles and Mechanisms of Circular RNA in Human Cancers</p>

Tang

Hann

2020

OTT

136

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Circular RNA (circRNA) is an intriguing class of RNA with covalently closedloop structure and is highly stable and conservative. As new members of the ncRNAs, the function, mechanism, potential diagnostic biomarker, and therapeutic target have raised increased attention. Most circRNAs are presented with characteristics of abundance, stability, conservatism, and often exhibiting tissue/developmental-stage-specific manner. Over 30,000 circRNAs have been identified with their unique structures to maintain stability more easily than linear RNAs. An increased numbers of circRNAs are dysregulated and involved in several biological processes of malignance, such as tumorigenesis, growth, invasion, metastasis, apoptosis, and vascularization. Emerging evidence suggests that circRNAs play important roles by acting as miRNA sponge or protein scaffolding, autophagy regulators, and interacting with RNA-binding protein (RBP), which may potentially serve as a novel promising biomarker for prevention, diagnosis and therapeutic target for treatment of human cancer with great significance either in scientific research or clinic arena. This review introduces concept, major features of circRNAs, and mainly describes the major biological functions and clinical relevance of circRNAs, as well as expressions and regulatory mechanisms in various types of human cancer, including pathogenesis, mode of action, potential target, signaling regulatory pathways, drug resistance, and therapeutic biomarkers. All of which provide evidence for the potential utilities of circRNAs in the diagnosis and treatment of cancer.

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Circular RNAs in hepatocellular carcinoma: Functions and implications

Cited by 109 publications

References 78 publications

Tumor‐suppressive circular RNAs: Mechanisms underlying their suppression of tumor occurrence and use as therapeutic targets

Tumor‐suppressive circular RNAs: Mechanisms underlying their suppression of tumor occurrence and use as therapeutic targets

Circular RNA circARNT2 Suppressed The Sensitivity of Hepatocellular Carcinoma Cells to Cisplatin by Targeting The miR-155-5p/PDK1 Axis

<p>Biological Roles and Mechanisms of Circular RNA in Human Cancers</p>

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