TLR7 agonist induced repression of hepatocellular carcinoma via the TLR7-IKK-NF-κB-IL6 signaling pathway

Ren, Xingbin; Wang, Fei; Ji, Baifeng; Gao, Chunhai

doi:10.3892/ol.2016.4329

Cited by 13 publications

(11 citation statements)

References 23 publications

(28 reference statements)

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“…The HH signaling pathway may also induce TGF-β signaling that further activates MAP3K7 (28). The IKK-NF-κB signaling pathway upregulates the expression of Snail2 (29). Ma et al reported that activated HH in CAF can promote the invasion and metastasis of tumor cells via paracrine action (30).…”

Section: Discussionmentioning

confidence: 99%

Prometastatic mechanisms of CAF-mediated EMT regulation in pancreatic cancer cells

Shan

Chen

et al. 2016

International Journal of Oncology

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Tumor metastasis are accompanied by the EMT (epithelial-mesenchymal transition)-MET (mesenchymal-epithelial transition) two-step process. In this study, we investigated the importance of cancer associated fibroblasts (CAF) in the process. First, the primary cultures of isolated pancreatic CAF, fibroblasts of normal pancreatic tissues (NF), and normal hepatic stellate cells (HSF) were identified and verified via the expression of α-SMA and vimentin. Using an indirect three-dimensional co-culture model, the morphological changes were observed by light microscopy and laser scanning confocal microscopy. The invasive and migration capacity of pancreatic cancer cells was determined by Transwell chamber migration assay or scratch assay. The mRNA and protein expression levels of E-cadherin, vimentin, and Gli1 were determined by RT-PCR and western blotting. Primary cultures of isolated CAF, NF, HSF showed satisfactory growth with active proliferation. Indirect co-culture with CAF, BxPc-3 and Panc-1 cells showed significant partial EMT, reduced E-cadherin expression, and enhanced vimentin expression as compared with the single culture and NF/HSF co-culture groups, with corresponding increases in migratory and invasive capacities. PCR and western blotting results showed that mRNA and protein expression levels of Gli1 in CAF and Snail in cancer cells were increased. This process could be reversed by inhibition of hedgehog (HH) signaling in CAF. In the tumor microenvironment, activation of CAF is the key event in mediating partial EMT, and its mechanism may be associated with paracrine action after activation of HH signaling in CAF.

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Section: Discussionmentioning

confidence: 99%

Prometastatic mechanisms of CAF-mediated EMT regulation in pancreatic cancer cells

Shan

Chen

et al. 2016

International Journal of Oncology

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“…Interestingly, other circular RNAs and microRNAs act as post-transcriptional modifiers of genes linked to the IKK/NF-κB signaling pathway in the liver [47]. Moreover, dysregulation of the IKK-NF-κB-IL-6 signaling pathway has been linked to the development of HCC [48,49].…”

Section: Discussionmentioning

confidence: 99%

Impact of circ-0000221 in the Pathogenesis of Hepatocellular via Modulation of miR-661–PTPN11 mRNA Axis

et al. 2022

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Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in Egypt. A deep understanding of the molecular events occurring in HCC can facilitate the development of novel diagnostic and/or therapeutic approaches. In the present study, we describe a novel axis of hsa-circ-0000221–miR-661–PTPN11 mRNA proposed by in silico and in vitro analysis and its role in HCC pathogenesis. We observe a reduction in the expression levels of hsa-circ-0000221 and PTPN11 mRNA in HCC patients’ sera tested compared with control subjects. The reduction occurs with a concomitant increase in the expression of miR-661. Furthermore, the introduction of exogenous hsa-circ-0000221 into Hep-G2 or SNU449 cell lines results in detectable decrease in cellular viability and an increase in apoptotic manifestations that is associated with G1 accumulation and CCDN1 overexpression. Altogether, these findings indicate the tumor-suppressive role of hsa-circ-0000221 in HCC, which acts through miR-661 inhibition, along with a subsequent PTPN11 mRNA increase, where PTPN11 is known to inhibit cell proliferation in many forms of cancer. Our study encourages further investigation of the role of circRNAs in cancer and their potential use as molecular biomarkers.

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“…TLR7 is a member of the TLR family that acts as a pattern recognition receptor and is expressed on the membrane of endosomes. TLR7 activation by ssRNA of virals and nucleic acids can induce the expression of type I interferon and inflammatory cytokines, and activate other immune cells through several signaling pathways, such as the NF-κB signaling pathway [ 34 , 35 ]. Considering the powerful immune regulatory function of TLR7, the agonists of TLR7 have been approved for topical application in cancer treatment [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of key genes as predictive biomarkers for osteosarcoma metastasis using translational bioinformatics

Ding

Tian

et al. 2021

Cancer Cell Int

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Background Osteosarcoma (OS) metastasis is the most common cause of cancer-related mortality, however, no sufficient clinical biomarkers have been identified. In this study, we identified five genes to help predict metastasis at diagnosis. Methods We performed weighted gene co-expression network analysis (WGCNA) to identify the most relevant gene modules associated with OS metastasis. An important machine learning algorithm, the support vector machine (SVM), was employed to predict key genes for classifying the OS metastasis phenotype. Finally, we investigated the clinical significance of key genes and their enriched pathways. Results Eighteen modules were identified in WGCNA, among which the pink, red, brown, blue, and turquoise modules demonstrated good preservation. In the five modules, the brown and red modules were highly correlated with OS metastasis. Genes in the two modules closely interacted in protein–protein interaction networks and were therefore chosen for further analysis. Genes in the two modules were primarily enriched in the biological processes associated with tumorigenesis and development. Furthermore, 65 differentially expressed genes were identified as common hub genes in both WGCNA and protein–protein interaction networks. SVM classifiers with the maximum area under the curve were based on 30 and 15 genes in the brown and red modules, respectively. The clinical significance of the 45 hub genes was analyzed. Of the 45 genes, 17 were found to be significantly correlated with survival time. Finally, 5/17 genes, including ADAP2 (P = 0.0094), LCP2 (P = 0.013), ARHGAP25 (P = 0.0049), CD53 (P = 0.016), and TLR7 (P = 0.04) were significantly correlated with the metastatic phenotype. In vitro verification, western blotting, wound healing analyses, transwell invasion assays, proliferation assays, and colony formation assays indicated that ARHGAP25 promoted OS cell migration, invasion, proliferation, and epithelial–mesenchymal transition. Conclusion We identified five genes, namely ADAP2, LCP2, ARHGAP25, CD53, and TLR7, as candidate biomarkers for the prediction of OS metastasis; ARHGAP25 inhibits MG63 OS cell growth, migration, and invasion in vitro, indicating that ARHGAP25 can serve as a promising specific and prognostic biomarker for OS metastasis.

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TLR7 agonist induced repression of hepatocellular carcinoma via the TLR7-IKK-NF-κB-IL6 signaling pathway

Cited by 13 publications

References 23 publications

Prometastatic mechanisms of CAF-mediated EMT regulation in pancreatic cancer cells

Prometastatic mechanisms of CAF-mediated EMT regulation in pancreatic cancer cells

Impact of circ-0000221 in the Pathogenesis of Hepatocellular via Modulation of miR-661–PTPN11 mRNA Axis

Identification of key genes as predictive biomarkers for osteosarcoma metastasis using translational bioinformatics

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