The Potential Role of circRNA in Tumor Immunity Regulation and Immunotherapy

Xu, Zihao; Li, Peiyao; Фан, Ли; Wu, Minghua

doi:10.3389/fimmu.2018.00009

Cited by 175 publications

(267 citation statements)

References 105 publications

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“…Studies have shown that exon-derived circRNAs have miRNA response elements on their surface that specifically bind to miRNAs and regulate downstream gene expression. 3 At present, there are only a few research articles on the relationship between circRNA and liver disease. The existing papers mainly focus on the field of primary liver cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Circular RNA (circRNA) is one of the latest areas of focus in the field of non‐coding RNA (ncRNA) research. The study of circRNAs has allowed for significant advances in the elucidation of disease pathogenesis, development of diagnostic biomarkers, and development of therapeutic targets, particularly in tumor biology, but there have been very few reports on their roles in the area of liver fibrosis. This study intends to further study the role of circRNA on the pathogenesis of liver fibrosis, in order to gain new insight for future studies on liver fibrosis, and to find new strategies for liver fibrosis treatment.…”

mentioning

confidence: 99%

“…Circular RNA (circRNA) is one of the latest areas of focus in the field of non-coding RNA (ncRNA) research. The study of circRNAs has allowed for significant advances in the elucidation of disease pathogenesis, development of diagnostic biomarkers, and development of therapeutic targets, particularly in tumor biology, 3 but there have been very few reports on their roles in the area of liver fibrosis.…”

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confidence: 99%

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Differential expression of circular RNAs in hepatic tissue in a model of liver fibrosis and functional analysis of their target genes

Zhou

Qü

et al. 2018

Hepatology Research

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Aim To measure the expression profile of circular RNA (circRNA) in hepatic tissues in a liver fibrosis model and to explore their function using molecular biology and bioinformatic techniques. Methods The classic CCl4 mouse liver fibrosis model was established alongside a normal control group. The circRNA expression profile of hepatic tissue from the two groups was compared using a high‐throughput circRNA microarray. The differentially expressed circRNAs were identified, and real‐time quantitative polymerase chain reaction (RT‐qPCR) was used to verify a subset of the differentially expressed circRNAs (target genes). At the same time, the mouse oxidative stress injury, macrophage inflammation, and hepatic stellate cell activation models were established, and the expression of target circRNA in the above cells was measured by RT‐qPCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to predict the biological functions of target genes. Finally, one of the circRNAs was selected and its cellular function was verified using siRNA. Results A total of 10 389 circRNAs were analyzed by microarray. Compared with the normal group, there were 69 circRNAs that were differentially expressed in the liver fibrosis model group (>2‐fold differential expression, P < 0.05), of which 14 were upregulated and 55 were downregulated. Five circRNAs and their differential expression were verified by RT‐qPCR, and the findings were consistent with the microarray results. Of these, three circRNAs were differentially expressed (P < 0.05) in the JS1 model, one circRNA was differentially expressed (P < 0.05) in the AML12 model, and four circRNAs were differentially expressed (P < 0.05) in the RAW264.7 model. The GO analysis showed that the differentially expressed circRNAs might be involved in cell autophagy, composition of extracellular matrix components, synthesis and metabolism of retinoic acid, retinol dehydrogenase activity, ubiquitin‐like protein ligase activity, histone methylation, and other biological functions. The KEGG analysis showed that the target genes of the differentially expressed circRNAs might be involved in transforming growth factor‐β1/smads, Hippo, Rap1, vascular endothelial growth factor, and other signaling pathways. Lipofection experiments showed that the expression of α‐smooth muscle actin (α‐SMA) in JS1 cells increased significantly after the expression of mmu_circ_34116 was decreased. Conclusion The circRNA expression profile in liver fibrosis tissue shows significant changes. Partially differentially expressed circRNA could be involved in hepatic fibrosis related to hepatic oxidative stress injury, macrophage inflammation, and stellate cell activation. For instance, mmu_circ_34116 can significantly inhibit the activation of hepatic stellate cells.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Differential expression of circular RNAs in hepatic tissue in a model of liver fibrosis and functional analysis of their target genes

Zhou

Qü

et al. 2018

Hepatology Research

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“…Circular RNAs (circRNAs) are new class of noncoding RNAs (ncRNAs) and are hotspot in the field of RNA . CircRNA has a high tissue‐specific expression and stable structure .…”

Section: Introductionmentioning

confidence: 99%

“…Circular RNAs (circRNAs) are new class of noncoding RNAs (ncRNAs) and are hotspot in the field of RNA. 6 CircRNA has a high tissue-specific expression and stable structure. 7 CircRNA mediates gene expression at the level of posttranscription or transcription by interacting with alternative molecules.…”

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confidence: 99%

Circular RNA circ‐Ttc3 protects HaCaT cells from hypoxic injury by downregulation of miR‐449a

Wang

Liu

et al. 2020

IUBMB Life

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Background Pressure ulcer (PU) is a common complication of acute and long‐time hospitalization, especially in elderly patients. The incidence and prevalence of PU are swiftly fortifying. Currently, our purpose was to investigate the functional impacts of circ‐Ttc3 on PU. Methods HaCaT cells were pretreated under hypoxia condition. Cell counting kit 8 assay and flow cytometry were utilized to test HaCaT cell viability and apoptosis. Quantitative reverse transcription polymerase chain reaction was utilized to determine circ‐Ttc3 and miR‐449a expression. Western blot was performed to examine apoptosis‐associated proteins expression. Subsequently, the above‐described investigations were reperformed after miR‐449a upregulation. Results Hypoxia induced apoptosis and declined viability in HaCaT cells. Circ‐Ttc3 expression was enhanced after transfection with circ‐Ttc3 expressing vector. Overexpressing circ‐Ttc3 raised viability and reduced apoptosis in HaCaT cells. Moreover, miR‐449a expression was elevated by hypoxia and reversed by overexpressing circ‐Ttc3. And circ‐Ttc3 exerted its effect via downregulating miR‐449a. Finally, overexpressing circ‐Ttc3 activated nuclear factor kappa‐B (NF‐κB) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathways via downregulating miR‐449a. Conclusion Our data suggested that circ‐Ttc3 alleviated hypoxic injury and activated NF‐κB and PI3K/AKT pathways by downregulating miR‐449a in HaCaT cells.

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Chemokine‐Capturing Wound Contact Layer Rescues Dermal Healing

et al. 2021

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Excessive inflammation often impedes the healing of chronic wounds. Scavenging of chemokines by multiarmed poly(ethylene glycol)-glycosaminoglycan (starPEG-GAG) hydrogels has recently been shown to support regeneration in a diabetic mouse chronic skin wound model. Herein, a textile-starPEG-GAG composite wound contact layer (WCL) capable of selectively sequestering pro-inflammatory chemokines is reported. Systematic variation of the local and integral charge densities of the starPEG-GAG hydrogel component allows for tailoring its affinity profile for biomolecular signals of the wound milieu. The composite WCL is subsequently tested in a large animal (porcine) model of human wound healing disorders. Dampening excessive inflammatory signals without affecting the levels of pro-regenerative growth factors, the starPEG-GAG hydrogel-based WCL treatment induced healing with increased granulation tissue formation, angiogenesis, and deposition of connective tissue (collagen fibers). Thus, this biomaterials technology expands the scope of a new anti-inflammatory therapy toward clinical use.

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The Potential Role of circRNA in Tumor Immunity Regulation and Immunotherapy

Cited by 175 publications

References 105 publications

Differential expression of circular RNAs in hepatic tissue in a model of liver fibrosis and functional analysis of their target genes

Differential expression of circular RNAs in hepatic tissue in a model of liver fibrosis and functional analysis of their target genes

Circular RNA circ‐Ttc3 protects HaCaT cells from hypoxic injury by downregulation of miR‐449a

Chemokine‐Capturing Wound Contact Layer Rescues Dermal Healing

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