RESUMEN
Objective: With the number of patients with acute pancreatitis (AP) increasing year by year, it is pressing to explore new key genes and markers for the treatment of AP. miR-455-3p/solute carrier family 2 member 1 (Slc2a1) obtained through bioinformatics analysis may participate in the progression of AP. Materials and Methods: The C57BL/6 mouse model of AP was constructed for subsequent studies. Through bioinformatics analysis, the differentially expressed genes related to AP were screened and hub genes were identified. A caerulein-induced AP animal model was constructed to detect the pathological changes of mouse pancreas by HE staining. The concentrations of amylase and lipase were measured. Primary mouse pancreatic acinar cells were isolated and subjected to microscopy to observe their morphology. The enzymatic activities of trypsin and amylase were detected. The secretion of inflammatory cytokines in mouse were measured with the ELISA kits of TNF-α, IL-6 and IL-1ß to determine pancreatic acinar cell damage. A binding site between the Slc2a1 3' UTR region and the miR-455-3p sequence was verified by dual-luciferase reporter assay. The expression of miR-455-3p was quantified by qRT-PCR, and Slc2a1 were detected by western blot. Results: A total of five (Fyn, Gadd45a, Sdc1, Slc2a1, and Src) were identified by bioinformatics analysis, and miR-455-3p/Slc2a1 were further studied. HE staining results showed that the AP models were successfully established by caerulein induction. In mice with AP, the expression of miR-455-3p was reduced, while that of Slc2a1 was increased. In the caerulein-induced cell model, the expression of Slc2a1 was significantly reduced after intervention of miR-455-3p mimics, whereas increased after miR-455-3p inhibitor treatment. miR-455-3p decreased the secretion of inflammatory cytokines in the cell supernatant, reduced the activity of trypsin and amylase, and alleviated the cell damage induced by caerulein. In addition, Slc2a1 3'UTR region was bound by miR-455-3p, and its protein expression was also regulated. Conclusion: miR-455-3p alleviated caerulein-induced mouse pancreatic acinar cell damage by regulating the expression of Slc2a1.
Asunto(s)
MicroARNs , Pancreatitis , Animales , Ratones , Células Acinares , Enfermedad Aguda , Amilasas/efectos adversos , Ceruletida/efectos adversos , Citocinas/efectos adversos , Ratones Endogámicos C57BL , MicroARNs/genética , Pancreatitis/inducido químicamente , Tripsina/efectos adversosRESUMEN
The incidence and mortality of hepatic carcinoma (HCC) remain high, and early diagnosis of HCC is seen as a key approach in improving clinical outcomes. However, the sensitivity and specificity of current early screening methods for HCC are not satisfactory. In recent years, research around exosomal miRNA has gradually increased, and these molecules have emerged as attractive candidates for early diagnosis and treatment of HCC. This review summarizes the feasibility of using miRNAs in peripheral blood exosomes as early diagnostic tools for HCC.
RESUMEN
AURKA (aurora kinase A) has been confirmed as an oncogene in cancer development; however, its role and underlying mechanisms in the metastasis of hepatocellular carcinoma (HCC) remain unknown. In this study, We found that AURKA was up-regulated in HCC tissues and correlated with pathological stage and distant metastasis. Further found that AURKA was involved in the cancer metastases after radiation in HCC. While overexpression of AURKA induced epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) behaviors though PI3K/AKT pathway, silencing AURKA suppressed radiation-enhanced cell invasiveness of HCC. Taken together, our results suggested that AURKA contributed in metastasis of irradiated residul HCC though facilitating EMT and CSC properties, suggesting the potential clinical application of AURKA inhibitors in radiotherapy for patients with HCC.