Circular RNA as a Novel Biomarker and Therapeutic Target for HCC

Meng, Hongwu; Niu, Ruowen; Huang, Cheng; Li, Jun

doi:10.3390/cells11121948

Cited by 24 publications

(3 citation statements)

References 72 publications

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“…Numerous abnormally expressing miRNAs are associated with HCC initiation and progression [ 76 , 77 ]. Various studies have exposed the biological roles of lncRNAs as regulators of transcription, modulators of mRNA processing, and organizers of nuclear domains [ 76 , 77 , 78 , 79 ]. Compared with linear RNAs, circRNAs are more stable to exonuclease and ribonuclease, with conserved structure and stable sequence and tissue specificity [ 78 , 79 ].…”

Section: Characteristics and Classification Of Rnasmentioning

confidence: 99%

“…Various studies have exposed the biological roles of lncRNAs as regulators of transcription, modulators of mRNA processing, and organizers of nuclear domains [ 76 , 77 , 78 , 79 ]. Compared with linear RNAs, circRNAs are more stable to exonuclease and ribonuclease, with conserved structure and stable sequence and tissue specificity [ 78 , 79 ]. It has been shown that circRNAs play significant pathophysiological roles in the existence and development of alcoholic liver injury; hepatic fibrosis, HCC, and other liver diseases CircRNAs have also been confirmed to exert effects with respect to regulation of cellular metabolisms of HCC [ 78 ].…”

Section: Characteristics and Classification Of Rnasmentioning

confidence: 99%

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Function of the Long Noncoding RNAs in Hepatocellular Carcinoma: Classification, Molecular Mechanisms, and Significant Therapeutic Potentials

Khan

Zhang

2022

Bioengineering

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Hepatocellular carcinoma (HCC) is the most common and serious type of primary liver cancer. HCC patients have a high death rate and poor prognosis due to the lack of clear signs and inadequate treatment interventions. However, the molecular pathways that underpin HCC pathogenesis remain unclear. Long non-coding RNAs (lncRNAs), a new type of RNAs, have been found to play important roles in HCC. LncRNAs have the ability to influence gene expression and protein activity. Dysregulation of lncRNAs has been linked to a growing number of liver disorders, including HCC. As a result, improved understanding of lncRNAs could lead to new insights into HCC etiology, as well as new approaches for the early detection and treatment of HCC. The latest results with respect to the role of lncRNAs in controlling multiple pathways of HCC were summarized in this study. The processes by which lncRNAs influence HCC advancement by interacting with chromatin, RNAs, and proteins at the epigenetic, transcriptional, and post-transcriptional levels were examined. This critical review also highlights recent breakthroughs in lncRNA signaling pathways in HCC progression, shedding light on the potential applications of lncRNAs for HCC diagnosis and therapy.

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Section: Characteristics and Classification Of Rnasmentioning

confidence: 99%

Section: Characteristics and Classification Of Rnasmentioning

confidence: 99%

Function of the Long Noncoding RNAs in Hepatocellular Carcinoma: Classification, Molecular Mechanisms, and Significant Therapeutic Potentials

Khan

Zhang

2022

Bioengineering

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“…Circular RNAs (circRNAs), characterized as noncoding RNAs with a closed-loop structure, regulate biological processes by acting as sponges for microRNAs (miR-NAs) or binding to proteins [14,15]. Many circRNAs are involved in cell proliferation, differentiation, apoptosis, invasion, stemness and resistance to therapy of HCC [16][17][18]. For instance, Huang et al indicated that circular RNA circMET drives immunosuppression and anti-PD1 therapy resistance in HCC via the miR-30-5p/snail/ dipeptidyl peptidase 4(DPP4) axis [19].…”

Section: Introductionmentioning

confidence: 99%

Exosome-derived circCCAR1 promotes CD8 + T-cell dysfunction and anti-PD1 resistance in hepatocellular carcinoma

Chen

Zhao

et al. 2023

Mol Cancer

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Background Circular RNAs (circRNAs) can be encapsulated into exosomes to participate in intercellular communication, affecting the malignant progression of a variety of tumors. Dysfunction of CD8 + T cells is the main factor in immune escape from hepatocellular carcinoma (HCC). Nevertheless, the effect of exosome-derived circRNAs on CD8 + T-cell dysfunction needs further exploration. Methods The effect of circCCAR1 on the tumorigenesis and metastasis of HCC was assessed by in vitro and in vivo functional experiments. The function of circCCAR1 in CD8 + T-cell dysfunction was measured by enzyme-linked immunosorbent assay (ELISA), western blotting and flow cytometry. Chromatin immunoprecipitation, biotinylated RNA pull-down, RNA immunoprecipitation, and MS2 pull-down assays were used to the exploration of mechanism. A mouse model with reconstituted human immune system components (huNSG mice) was constructed to explore the role of exosomal circCCAR1 in the resistance to anti-PD1 therapy in HCC. Results Increased circCCAR1 levels existed in tumor tissues and exosomes in the plasma of HCC patients, in the culture supernatant and HCC cells. CircCCAR1 accelerated the growth and metastasis of HCC in vitro and in vivo. E1A binding protein p300 (EP300) and eukaryotic translation initiation factor 4A3 (EIF4A3) promoted the biogenesis of circCCAR1, and Wilms tumor 1-associated protein (WTAP)-mediated m6A modification enhanced circCCAR1 stability by binding insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3). CircCCAR1 acted as a sponge for miR-127-5p to upregulate its target WTAP and a feedback loop comprising circCCAR1/miR-127-5p/WTAP axis was formed. CircCCAR1 is secreted by HCC cells in a heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1)-dependent manner. Exosomal circCCAR1 was taken in by CD8 + T cells and caused dysfunction of CD8 + T cells by stabilizing the PD-1 protein. CircCCAR1 promoted resistance to anti-PD1 immunotherapy. Furthermore, increased cell division cycle and apoptosis regulator 1 (CCAR1) induced by EP300 promoted the binding of CCAR1 and β-catenin protein, which further enhanced the transcription of PD-L1. Conclusions The circCCAR1/miR-127-5p/WTAP feedback loop enhances the growth and metastasis of HCC. Exosomal circCCAR1 released by HCC cells contributes to immunosuppression by facilitating CD8 + T-cell dysfunction in HCC. CircCCAR1 induces resistance to anti-PD1 immunotherapy, providing a potential therapeutic strategy for HCC patients.

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HuR-induced circ_0082319 contributes to hepatocellular carcinoma by elevating PTK2 through miR-505-3p

Qin,

Liu,

Chen

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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Circular RNA as a Novel Biomarker and Therapeutic Target for HCC

Cited by 24 publications

References 72 publications

Function of the Long Noncoding RNAs in Hepatocellular Carcinoma: Classification, Molecular Mechanisms, and Significant Therapeutic Potentials

Function of the Long Noncoding RNAs in Hepatocellular Carcinoma: Classification, Molecular Mechanisms, and Significant Therapeutic Potentials

Exosome-derived circCCAR1 promotes CD8 + T-cell dysfunction and anti-PD1 resistance in hepatocellular carcinoma

HuR-induced circ_0082319 contributes to hepatocellular carcinoma by elevating PTK2 through miR-505-3p

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