Pediatric cancers are the driving cause of death for children and adolescents. Due to safety requirements and considerations, treatment strategies and drugs for pediatric cancers have been so far scarcely studied. It is well known that tumor cells tend to progressively evade cell death pathways, which is known as apoptosis resistance, one of the hallmarks of cancer, dominating tumor drug resistance. Recently, treatments targeting nonapoptotic cell death have drawn great attention. Pyroptosis, a newly specialized form of cell death, acts as a critical physiological regulator in inflammatory reaction, cell development, tissue homeostasis and stress response. The action in different forms of pyroptosis is of great significance in the therapy of pediatric cancers. Pyroptosis could be induced and consequently modulate tumorigenesis, progression, and metastasis if treated with local or systemic therapies. However, excessive or uncontrolled cell death might lead to tissue damage, acute inflammation, or even cytokine release syndrome, which facilitates tumor progression or recurrence. Herein, we aimed to describe the molecular mechanisms of pyroptosis, to highlight and discuss the challenges and opportunities for activating pyroptosis pathways through various oncologic therapies in multiple pediatric neoplasms, including osteosarcoma, neuroblastoma, leukemia, lymphoma, and brain tumors.
Background Emerging studies have explored the prognostic value of MIR31HG in cancers, but its role remains elusive. Herein, we aimed to summarize the prognostic potential of MIR31HG in this study. Methods Several databases were searched for literature retrieval on Dec 5, 2019. Overall and subgroup analyses were conducted to measure the relationship between MIR31HG expression and clinical outcomes. Moreover, GEPIA was applied for validation of prognostic value of MIR31HG in tumor patients in TCGA dataset. Results Overall, seventeen studies with 2,573 patients were enrolled. Compared to counterparts, those patients with high MIR31HG expression tended to have shorter RFS. Notably, MIR31HG overexpression predicted unfavorable OS in lung cancer. By contrast, gastrointestinal cancer patients with elevated MIR31HG expression predicted better OS and disease-free survival. Additionally, MIR31HG overexpression was significantly associated with worse clinicopathological features including advanced tumor stage and LNM in lung cancer, but favorable clinical characteristics in gastrointestinal cancer. Moreover, the positive association between MIR31HG and OS in lung cancer was further confirmed in TCGA dataset. Conclusion Overexpression of MIR31HG suggested remarkable association with poor prognosis in terms of OS, tumor stage, and LNM in lung cancer, but favorable prognosis in gastrointestinal cancer. Therefore, MIR31HG may serve as a promising prognostic biomarker in multiple cancers.
BackgroundArterial calcification is an important pathological change of diabetic vascular complication. Osteoblastic differentiation of vascular smooth muscle cells (VSMCs) plays an important cytopathologic role in arterial calcification. The glucagon-like peptide-1 receptor agonists (GLP-1RA), a novel type of antidiabetic drugs, exert cardioprotective effects through the GLP-1 receptor (GLP-1R). However, the question of whether or not GLP-1RA regulates osteoblastic differentiation and calcification of VSMCs has not been answered, and the associated molecular mechanisms have not been examined.MethodsCalcifying VSMCs (CVSMCs) were isolated from cultured human arterial smooth muscle cells through limiting dilution and cloning. The extent of matrix mineralization was measured by Alizarin Red S staining. Protein expression and phosphorylation were detected by Western blot. Gene expression of receptor activator of nuclear factor-κB ligand (RANKL) was silenced by small interference RNA (siRNA).ResultsExenatide, an agonist of GLP-1 receptor, attenuated β-glycerol phosphate (β-GP) induced osteoblastic differentiation and calcification of human CVSMCs in a dose- and time-dependent manner. RANKL siRNA also inhibited osteoblastic differentiation and calcification. Exenatide decreased the expression of RANKL in a dose-dependent manner. 1,25 vitD3 (an activator of RANKL) upregulated, whereas BAY11-7082 (an inhibitor of NF-κB) downregulated RANKL, alkaline phosphatase (ALP), osteocalcin (OC), and core binding factor α1 (Runx2) protein levels and reduced mineralization in human CVSMCs. Exenatide decreased p-NF-κB and increased p-AMPKα levels in human CVSMCs 48 h after treatment. Significant decrease in p-NF-κB (p-Ser276, p-Ser536) level was observed in cells treated with exenatide or exenatide + BAY11-7082.ConclusionGLP-1RA exenatide can inhibit human VSMCs calcification through NF-κB/RANKL signaling.
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