Progress and prospects of circular RNAs in Hepatocellular carcinoma: Novel insights into their function

Hu, Ji; Peng, Li; Yang, Song; Ge, Yunxuan; Meng, Xiao‐Ming; Huang, Cheng; Li, Jun; Xu, Tao

doi:10.1002/jcp.26154

Cited by 48 publications

(40 citation statements)

References 126 publications

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“…Hepatocellular carcinoma, the most predominant type of primary liver cancer, is one of the leading causes of cancer-related death and arouses global concern in recent years ( Abdalla et al, 2018 ; Hu et al, 2018 ; Jin et al, 2018 ). Because most (more than 80%) of patients with HCC are diagnosed at a late stage of the disease, potentially curative therapies (including ablation, chemotherapy, proton beam therapy, chemoembolization, and targeted drug therapy) are often less effective and only extend the overall survival by a short time ( Llovet et al, 2008 ; Gao et al, 2014 ; Xiang et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Disruption of PD-1 Enhanced the Anti-tumor Activity of Chimeric Antigen Receptor T Cells Against Hepatocellular Carcinoma

et al. 2018

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Cancer immunotherapy has made unprecedented breakthrough in the fields of chimeric antigen receptor-redirected T (CAR T) cell therapy and immune modulation. Combination of CAR modification and the disruption of endogenous inhibitory immune checkpoints on T cells represent a promising immunotherapeutic modality for cancer treatment. However, the potential for the treatment of hepatocellular carcinoma (HCC) has not been explored. In this study, the gene expressing the programmed death 1 receptor (PD-1) on the Glypican-3 (GPC3)-targeted second-generation CAR T cells employing CD28 as the co-stimulatory domain was disrupted using the CRISPR/Cas9 gene-editing system. It was found that, in vitro, the CAR T cells with the deficient PD-1 showed the stronger CAR-dependent anti-tumor activity against native programmed death 1 ligand 1-expressing HCC cell PLC/PRF/5 compared with the wild-type CAR T cells, and meanwhile, the CD4 and CD8 subsets, and activation status of CAR T cells were stable with the disruption of endogenous PD-1. Additionally, the disruption of PD-1 could protect the GPC3-CAR T cells from exhaustion when combating with native PD-L1-expressing HCC, as the levels of Akt phosphorylation and anti-apoptotic protein Bcl-xL expression in PD-1 deficient GPC3-CAR T cells were significantly higher than those in wild-type GPC3-CAR T cells after coculturing with PLC/PRF/5. Furthermore, the in vivo anti-tumor activity of the CAR T cells with the deficient PD-1 was investigated using the subcutaneous xenograft tumor model established by the injection of PLC/PRF/5 into NOD-scid-IL-2Rγ-/- (NSG) mice. The results indicated that the disruption of PD-1 enhanced the in vivo anti-tumor activity of CAR T cells against HCC, improved the persistence and infiltration of CAR T cells in the NSG mice bearing the tumor, and strengthened the inhibition of tumor-related genes expression in the xenograft tumors caused by the GPC3-CAR T cells. This study indicates the enhanced anti-tumor efficacy of PD-1-deficient CAR T cells against HCC and suggests the potential of precision gene editing on the immune checkpoints to enhance the CAR T cell therapies against HCC.

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Section: Introductionmentioning

confidence: 99%

Disruption of PD-1 Enhanced the Anti-tumor Activity of Chimeric Antigen Receptor T Cells Against Hepatocellular Carcinoma

et al. 2018

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“…Hepatocellular carcinoma (HCC) is a most common malignancy and is a leading cause of cancer‐related death in the world . HCC progression can be attributed to a series of complex factors, such as gene regulation alteration and histone modification .…”

Section: Introductionmentioning

confidence: 99%

“…Hepatocellular carcinoma (HCC) is a most common malignancy and is a leading cause of cancer-related death in the world. 1 HCC progression can be attributed to a series of complex factors, such as gene regulation alteration and histone modification. 2 Although therapies such as resection, transplantation and ablation have been widely put into use, the prognosis of HCC patients is still poor because of the high metastasis frequency.…”

Section: Introductionmentioning

confidence: 99%

Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR‐375/JAK2

Cao

Wang

et al. 2018

Immunol Cell Biol

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In this study, we sought to predict the effects of a certain circular RNA (circRNA), hsa_circ_101280 (also known as hsa_circ_0100929 and hsa_circ_SLAIN1), on hepatocellular carcinoma (HCC) cells and to determine the potential mechanism. After screening differentially expressed circRNAs in HCC tissues through Gene Expression Omnibus data analysis, hsa_circ_101280 was found to be highly expressed, and its high expression was verified in HCC cell lines with qRT‐PCR along with the low expression of its downstream miRNA miR‐375. Colony formation and flow cytometry assays showed that both hsa_circ_101280 silencing and miR‐375 overexpression restrained proliferation and promoted apoptosis in HCC cells. JAK2 was identified as a downstream mRNA target of miR‐375 by RNA pull‐down and dual‐luciferase reporter gene assays, its expression in HCC cell lines were positively regulated by hsa_circ_101280 and negatively by miR‐375 expression. Furthermore, the silencing of hsa_circ_101280 significantly inhibited the growth of HCC xenografts in nude mice, with the downregulated expression of JAK2. Overall, both the in vitro and in vivo studies revealed that hsa_circ_101280 largely facilitated the tumorigenesis of HCC, characterized by the promoted proliferation and suppressed apoptosis of HCC cells, by sponging miR‐375 and upregulating JAK2.

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“…For instance, hsa_circ_0005075, hsa_circ_0001649, hsa_circ_0005986, hsa_circ_0004018, circRNA_000839 and circMTO1 may be novel biomarker of hepatocellular carcinoma. 62 , 63 , 64 , 65 , 66 , 71 , 72 hsa_circ_0013958 and hsa_circ_002059 may be the potential marker of lung adenocarcinoma and gastric carcinoma respectively. 73 , 74 …”

Section: Circrna a Promising Biomarker Especially In Exosomesmentioning

confidence: 99%

The novel roles of circular RNAs in metabolic organs

Zhang

Guo

2018

Genes & Diseases

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Circular RNAs (circRNAs) with a covalently closed loop structure which was different with linear RNAs, recently re-merged as novel regulator and exerted function in multiple biological processes. Through deep RNA sequencing (RNA-seq) technology coupled with bioinformatic analyses, a number of circRNAs has been identified. Moreover, circRNAs exhibit tissue- and development-specific expression indicating their potential biological significance. Actually, function of circRNAs as miRNA sponge has been well demonstrated in some diseases, besides, circRNAs also could function as RNA binding protein sponge and regulate alternative splicing and gene transcription. Notably, Emerging evidences showed that circRNAs played a pivotal role on the development of diseases including atherosclerotic vascular disease, neurological disorders and liver diseases, and served as diagnostic or predictive biomarkers of some diseases. This review mainly discusses the current advance of circRNAs as regulator involved in many diseases, and highlights circRNAs which have been well elucidated biological and pathogenic mechanism.

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Progress and prospects of circular RNAs in Hepatocellular carcinoma: Novel insights into their function

Cited by 48 publications

References 126 publications

Disruption of PD-1 Enhanced the Anti-tumor Activity of Chimeric Antigen Receptor T Cells Against Hepatocellular Carcinoma

Disruption of PD-1 Enhanced the Anti-tumor Activity of Chimeric Antigen Receptor T Cells Against Hepatocellular Carcinoma

Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR‐375/JAK2

The novel roles of circular RNAs in metabolic organs

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