Coptisine Blocks Secretion of Exosomal <i>circCCT3</i> from Cancer-Associated Fibroblasts to Reprogram Glucose Metabolism in Hepatocellular Carcinoma

Lv, Baowei; Zhu, Weiwei; Feng, Chunqing

doi:10.1089/dna.2020.6058

Cited by 22 publications

(15 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 9 Accruing evidence has shown that circRNAs function as modulators in cancer development, and they may be novel biomarkers and therapeutic targets. 10 CircCCT3 (circBase ID: hsa_circ_0004680) is originated from exons 3-5 and introns 3-4 of chaperonin containing TCP1 subunit 3 (CCT3) by back-splicing, 11 and is identified to be involved in the progression of hepatocellular carcinoma 11 and colorectal cancer. 12 So far, the role of CircCCT3 on PC progression has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

CircCCT3 Acts as a Sponge of miR-613 to Promote Tumor Growth of Pancreatic Cancer Through Regulating VEGFA/VEGFR2 Signaling

et al. 2021

View full text Add to dashboard Cite

Background: Circular RNAs (CircRNAs) have been recently implicated in the progression of pancreatic cancer (PC). Aims: To investigate the involvement of CircCCT3 in PC and studying its interactions and functioning during the progression of PC in vitro and in vivo, using methods of molecular biology and bioinformatics. Study Desig n: Experimental study. Methods: The expressions of CircCCT3 and miR-613 in pancreatic carcinoma tissues and cell lines were evaluated by quantitative real-time polymerase chain reaction (PCR). The relationship between clinical pathologic features as well as the survival rate and CircCCT3 expression was analyzed with chi-square test and the Kaplan–Meier method. CCK-8, wound healing, transwell assays, and the fluorescein isothiocyanate-AnnexinV/propidium iodide (FITC-AnnexinV/PI) assay were used to assess cell proliferation, migration, invasion, and apoptosis after CircCCT3 overexpression or downregulation. The Dual-Luciferase reporter assay, RNA immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization (FISH) assays were performed to validate the potential interaction of CircCCT3, miR-613, and vascular endothelial growth factor (VEGFA). The nude mouse xenograft tumor assay was used to detect CircCCT3 effects on pancreatic tumorigenesis in vivo. Western blotting analysis was performed to examine the VEGFA and the vascular endothelial growth factor receptor 2 (VEGFR2) protein expressions following. Results: CircCCT3 expression was significantly increased in PC tissues (3.41 ± 0.57 vs. 1.00 ± 0.10, P < .01) and cell lines (Patu8988 2.57 ± 0.20; SW1990 2.88 ± 0.10; BxPC-3 2.45 ± 0.20; Panc02 2.99 ± 0.10 vs. H6c7 1.00 ± 0.10; all P < .001). CircCCT3 expression was negatively correlated with miR-613 expression. PC patients with high CircCCT3 expression exhibited significantly poorer overall survival rate than those patients with low CircCCT3 expression ( P = .013). Moreover, it was found that CircCCT3 promoted cell proliferation, migration, and invasion, and inhibited cell apoptosis in PC cells. The CircCCT3 acted as a sponge for the miR-613 to facilitate VEGFA and VEGFR2 expression. si-CirCCT3 also inhibited tumor growth of PC in nude mice. si-CircCCT3 reduced VEGFA and VEGFR2 expression, whereas overexpression of CircCCT3 increased VEGFA and VEGFR2 expression. Conclusion: Increased CircCCT3 suggests a poor prognosis for PC patients and promotes the migration and invasion through targeting VEGFA/VEGFR2 signaling. CircCCT3 may serve as a potential and promising therapeutic target for PC treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

CircCCT3 Acts as a Sponge of miR-613 to Promote Tumor Growth of Pancreatic Cancer Through Regulating VEGFA/VEGFR2 Signaling

et al. 2021

View full text Add to dashboard Cite

show abstract

“…A clinical study confirmed the therapeutic advantage of combined conophylline and sorafenib treatment in advance HCC ( 52 ). Exosomal circCCT3 derived from CAFs can stimulate the activity of glucose metabolism-related gene HK2 and further affect the glucose metabolism of HCC cells ( 151 ), which is blocked by coptisine, the main component of Chelidonium majus L., Corydalis uanhusuo W. T. Wang, and Coptis japonica Makino ( 152 ). Glycyrrhizin and its metabolites glycyrrhetinic acid can attenuate non-alcoholic steatohepatitis-induced liver fibrosis, which is mediated by suppression of NLR family pyrin domain-containing 3 (NLRP3) inflammasome and restoration of bile acid homeostasis ( 153 ).…”

Section: Traditional Chinese Medicines As Resources Of Treating Liver Fibrosismentioning

confidence: 99%

The Role of Cancer-Associated Fibroblasts in Hepatocellular Carcinoma and the Value of Traditional Chinese Medicine Treatment

Jia¹,

Liang

Cheng³

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

Invasion and metastasis are the main reasons for the high mortality of liver cancer, which involve the interaction of tumor stromal cells and malignant cells. Cancer-associated fibroblasts (CAFs) are one of the major constituents of tumor stromal cells affecting tumor growth, invasion, and metastasis. The heterogeneous properties and sources of CAFs make both tumor-supporting and tumor-suppression effects possible. The mechanisms for CAFs in supporting hepatocellular carcinoma (HCC) progression can be categorized into upregulated aggressiveness and stemness, transformed metabolism toward glycolysis and glutamine reductive carboxylation, polarized tumor immunity toward immune escape of HCC cells, and increased angiogenesis. The tumor-suppressive effect of fibroblasts highlights the functional heterogenicity of CAF populations and provides new insights into tumor–stromal interplay mechanisms. In this review, we introduced several key inflammatory signaling pathways in the transformation of CAFs from normal stromal cells and the heterogeneous biofunctions of activated CAFs. In view of the pleiotropic regulation properties of traditional Chinese medicine (TCM) and heterogeneous effects of CAFs, we also introduced the application and values of TCM in the treatment of HCC through targeting CAFs.

show abstract

“…circCCT3 is formed from chaperonin containing TCP1 subunit 3 (CCT3) [ 8 ]. Although circCCT3 is involved in tumorigenesis and metastasis of colorectal cancer (CRC) and hepatocellular carcinoma (HCC), the potential mechanism by which circCCT3 regulates metastasis of NSCLC remains to be clarified [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

circCCT3 Enhances Invasion and Epithelial-Mesenchymal Transition (EMT) of Non-Small-Cell Lung Cancer (NSCLC) via the miR-107/Wnt/FGF7 Axis

Yang

et al. 2022

Journal of Oncology

View full text Add to dashboard Cite

Background. CircRNAs play a role in a variety of biological processes, including tumorigenesis. circCCT3 has been shown to regulate cancer initiation and progression. Unfortunately, whether circCCT3 is involved in non-small-cell lung cancer (NSCLC) metastasis remains unclear. Methods. Our study utilized RT-qPCR to examine gene expression levels. A transwell assay was used to measure invasion ability of cells. Starbase software and TargetScan software were used to predict target genes. Results. circCCT3 knockdown attenuated invasion and epithelial-mesenchymal transition (EMT) of A549 and Calu-1 cells. miR-107 mimics could rescue circCCT3-induced invasion and EMT. Next, miR-107 mimics and circCCT3 knockdown suppressed Wnt3a and FGF7 expression. An miR-107 inhibitor promoted Wnt3a and FGF7 expressions. Finally, FGF7 greatly restored miR-107-inhibited invasion and EMT of A549 cells. Conclusion. Here, we reveal a molecular mechanism circCCT3/miR-107/Wnt/FGF7 responsible for NSCLC metastasis.

show abstract

Coptisine Blocks Secretion of Exosomal circCCT3 from Cancer-Associated Fibroblasts to Reprogram Glucose Metabolism in Hepatocellular Carcinoma

Cited by 22 publications

References 32 publications

CircCCT3 Acts as a Sponge of miR-613 to Promote Tumor Growth of Pancreatic Cancer Through Regulating VEGFA/VEGFR2 Signaling

CircCCT3 Acts as a Sponge of miR-613 to Promote Tumor Growth of Pancreatic Cancer Through Regulating VEGFA/VEGFR2 Signaling

The Role of Cancer-Associated Fibroblasts in Hepatocellular Carcinoma and the Value of Traditional Chinese Medicine Treatment

circCCT3 Enhances Invasion and Epithelial-Mesenchymal Transition (EMT) of Non-Small-Cell Lung Cancer (NSCLC) via the miR-107/Wnt/FGF7 Axis

Contact Info

Product

Resources

About