Exosome-transmitted circular RNA hsa_circ_0051443 suppresses hepatocellular carcinoma progression

Chen, Wei; Quan, Yingyao; Fan, Shaoyi; Wang, Hua; Liang, Jun; Huang, Li; Chen, Liuhua; Liu, Qi; He, Peiheng; Ye, Yibiao

doi:10.1016/j.canlet.2020.01.022

Cited by 213 publications

(170 citation statements)

References 33 publications

Supporting

Mentioning

152

Contrasting

Unclassified

Order By: Relevance

“…Further, we found that circ-LRIG3 was also upregulated in HCC plasma, the AUC value was 0.8681 (95%CI: 0.7843 ~ 0.9519), suggesting its great potential as a non-invasive diagnostic marker of HCC. Of note, recent studies show that some circRNAs are enriched and stable in exosomes [27,28], such as hsa_circ_0051443 [29], hsa_circ_100338 [30] and hsa_circ_0006156 [31]. Whether circ-LRIG3 also exists in exosomes is worth further study, in addition, the multi-center large-scale sample investigation is necessary to con rm the diagnostic and prognostic value of circ-LRIG3 in HCC.…”

Section: Discussionmentioning

confidence: 98%

A Novel Circular RNA circ-LRIG3 Facilitates the Malignant Progression of Hepatocellular Carcinoma by Modulating the EZH2/STAT3 Signaling

Sun

Gao

Zhou

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Circular RNA (circRNA) is emerging as an important player in human diseases, especially cancer. In our previous study, we identified a series of deregulated circRNAs in hepatocellular carcinoma (HCC) by performing circRNA microarray expression profile. Here, we aimed to explore the role of circ-LRIG3 (hsa_circ_0027345) in HCC.Methods: qRT-PCR and western blot were used to asses gene and protein expression, respectively. CCK-8, EdU and Transwell assays were used to detect cell proliferation, migration and invasion. GSEA software was applied to analyze the pathway related to circ-LRIG3. Co-IP, RIP and ChIP assays were used to identify the positive feedback axis of circ-LRIG3/EZH2/STAT3. Animal study was carried to test the role of circ-LRIG3 in vivo.Results: Circ-LRIG3 was notably upregulated in HCC and promoted HCC cell proliferation, migration, invasion and reduced apoptosis. Circ-LRIG3 formed a ternary complex with EZH2 and STAT3, facilitating EZH2-induced STAT3 methylation and subsequent phosphorylation, resulting in the activation of STAT3 signaling. In turn, activated STAT3 could directly bind to circ-LRIG3 promoter to increase circ-LRIG3 transcription activity, thus forming a positive feedback loop. The animal models showed that exogenous expression of circ-LRIG3 enhanced tumorigenicity and metastasis in vivo, whereas these effects were blocked after treatment with C188-9, a specific STAT3 small-molecule inhibitor. Clinically, high circ-LRIG3 was closely linked with aggressive clinicopathological features and was identified as an independent risk prognostic factor of overall survival. Importantly, plasma circ-LRIG3 was found to be a highly sensitive and specific non-invasive diagnostic indicator for HCC. Conclusions: Our study reveals the carcinogenic role of circ-LRIG3 in HCC, which may provide a new therapeutic target for HCC patients.

show abstract

Section: Discussionmentioning

confidence: 98%

A Novel Circular RNA circ-LRIG3 Facilitates the Malignant Progression of Hepatocellular Carcinoma by Modulating the EZH2/STAT3 Signaling

Sun

Gao

Zhou

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…circ-0051443 delivered by EVs in hepatocarcinoma cells was reported to reduce tumor progression and, in vivo, the size and weight of xenograft tumors. In this case, circRNA acted as a sponge of miR-331-3p, inhibiting expression of the BAK1 gene, an important cell death regulator [ 142 ]. EV circRNA was also found to play a role in chemoresistance.…”

Section: Engineering Ev-based Cancer Therapymentioning

confidence: 99%

Extracellular Vesicle-Based Nucleic Acid Delivery: Current Advances and Future Perspectives in Cancer Therapeutic Strategies

et al. 2020

View full text Add to dashboard Cite

Extracellular vesicles (EVs) are sophisticated and sensitive messengers released by cells to communicate with and influence distant and neighboring cells via selective transfer of bioactive content, including protein lipids and nucleic acids. EVs have therefore attracted broad interest as new and refined potential therapeutic systems in many diseases, including cancer, due to their low immunogenicity, non-toxicity, and elevated bioavailability. They might serve as safe and effective vehicles for the transport of therapeutic molecules to specific tissues and cells. In this review, we focus on EVs as a vehicle for gene therapy in cancer. We describe recent developments in EV engineering to achieve efficient intracellular delivery of cancer therapeutics and avoid off-target effects, to provide an overview of the potential applications of EV-mediated gene therapy and the most promising biomedical advances.

show abstract

“…Studies have shown that circRNAs are specifically expressed in peripheral blood of GC patients. 16 The stable loop structure of circRNAs extends their half-life, particularly in cell-free samples (such as blood, urine and saliva), whose expression is related to tumor progression, and can be used as a molecular marker specific for the diagnosis of GC. 3,16 Meanwhile, circRNAs have been reported to have a number of important roles including acting as protein sponges, serving as miRNA sponges, and being translated into proteins or peptides.…”

Section: Introductionmentioning

confidence: 99%

<p>Comprehensive Assessment of Plasma Circ_0004771 as a Novel Diagnostic and Dynamic Monitoring Biomarker in Gastric Cancer</p>

Yan

Kong

Qin

et al. 2020

OTT

View full text Add to dashboard Cite

Due to the lack of specific and sensitive detection indicators, most patients with GC are already in the advanced stage at the time of diagnosis. Therefore, it is urgent to search for effective diagnostic biomarkers that can be applied in clinic. Materials and Methods: We screened out circ_0004771 through circRNA sequencing. Exonuclease digestion assay, agarose gel electrophoresis (AGE) and Sanger sequencing verified the potential of circ_0004771 being a biomarker. Additionally, we established quantitative real-time fluorescent polymerase chain reaction (qRT-PCR) to detect the expression level of circ_0004771 and evaluated the methodology. What's more, we collected plasma samples from 120 GC patients, 40 superficial gastritis patients, 20 postoperative GC patients, 20 postoperative recurrence patients and 120 healthy donors. We constructed the receiver operating characteristic curve (ROC) to appraise its diagnostic efficacy. Results: The expression level of circ_0004771 is up-regulated in GC tissues, which is consistent with circRNA sequencing result (P=0.0001). Circ_0004771 can serve as a promising biomarker because of its stable structure and longer half-life. Plasma circ_0004771 expression is markedly richer in GC patients than that in normal people (P<0.0001), and the area under the ROC (AUC) is 0.831 (95% CI: 0.779-0.883). The diagnostic efficacy of circ_0004771 is higher than that of CEA (AUC=0.747, 95% CI: 0.686-0.808) and CA199 (AUC=0.508, 95% CI: 0.433-0.583). Higher diagnostic efficacy can be achieved by combination diagnosis for distinguishing GC patients from normal people (AUC=0.864). Besides, the expression level of circ_0004771 can distinguish GC patients from gastritis patients (AUC=0.845, 95% CI: 0.772-0.917). The plasma circ_0004771 expression in GC patients decreased to normal after surgery (P<0.0001). In addition, plasma circ_0004771 expression increased again in patients with postoperative recurrence. Conclusion: Plasma circ_0004771 is differentially expressed in GC patients, postoperative GC patients and patients with recurrence, suggesting that plasma circ_0004771 can be used as a novel diagnostic and dynamic monitoring biomarker in GC.

show abstract

Exosome-transmitted circular RNA hsa_circ_0051443 suppresses hepatocellular carcinoma progression

Cited by 213 publications

References 33 publications

A Novel Circular RNA circ-LRIG3 Facilitates the Malignant Progression of Hepatocellular Carcinoma by Modulating the EZH2/STAT3 Signaling

A Novel Circular RNA circ-LRIG3 Facilitates the Malignant Progression of Hepatocellular Carcinoma by Modulating the EZH2/STAT3 Signaling

Extracellular Vesicle-Based Nucleic Acid Delivery: Current Advances and Future Perspectives in Cancer Therapeutic Strategies

<p>Comprehensive Assessment of Plasma Circ_0004771 as a Novel Diagnostic and Dynamic Monitoring Biomarker in Gastric Cancer</p>

Contact Info

Product

Resources

About