MicroRNA-194-5p/Heparin-binding EGF-like growth factor signaling mediates dexamethasone-induced activation of pseudorabies virus in rat pheochromocytoma cells.

Pseudorabies virus (PRV) is a neurotropic virus, which infects a wide range of mammals. The activity of PRV is gradually suppressed in hosts that have tolerated the primary infection. Increased glucocorticoid levels resulting from stressful stimuli overcome repression of PRV activity. However, the host cell mechanism involved in the activation processes under stressful conditions remains unclear. In this study, infection of rat PC-12 pheochromocytoma cells with neuronal properties using PRV at a multiplicity of infection (MOI) = 1 for 24 h made the activity of PRV be the relatively repressed state, and then incubation with 0.5 µM of the corticosteroid dexamethasone (DEX) for 4 h overcomes the relative repression of PRV activity. RNA-seq deep sequencing and bioinformatics analyses revealed different microRNA and mRNA profiles of PC-12 cells with/without PRV and/or DEX treatment. qRT-PCR and western blot analyses confirmed the negative regulatory relationship of miRNA-194-5p and its target heparin-binding EGF-like growth factor (Hbegf); a dual-luciferase reporter assay revealed that Hbegf is directly targeted by miRNA-194-5p. Further, miRNA-194-5p mock transfection contributed to PRV activation, Hbegf was downregulated in DEX-treated PRV infection cells, and Hbegf overexpression contributed to returning activated PRV to the repression state. Moreover, miRNA-194-5p overexpression resulted in reduced levels of HBEGF, c-JUN, and p-EGFR, whereas Hbegf overexpression suppressed the reduction caused by miRNA-194-5p overexpression. Overall, this study is the first to report that changes in the miR-194-5p-HBEGF/EGFR pathway in neurons are involved in DEX-induced activation of PRV, laying a foundation for the clinical prevention of stress-induced PRV activation.

SOX2 Overlapping Transcript (SOX2-OT) Enhances the Lung Cancer Malignancy Through Interaction with miR-194-5p/SOX5 Axis.

Background: Lung cancer is one of the most common types of cancer and a leading cause of cancer-related deaths worldwide. Therefore, it is useful to know the biomarkers involved in the malignancy of lung cancer. Objectives: This study aimed to show that SOX2-OT as a long non-coding RNA (IncRNA) regulates gene expression via the SOX2-OT/miR-194-5p/SOX5 axis molecular pathway in lung cancer. Materials and Methods: A549 cells transfected with siRNA-SOX2-OT and the expression of SOX2-OT and miR-194-5p genes were analyzed by real-time PCR before and after transfection. In addition, the expression of the B-catenin, MMP9, phosphorylated and activated STAT3 (p-STAT3), SOX5, and VEGF proteins before and after transfection was investigated by Western blotting. Results: After using siRNA-SOX2-OT, an increase in the expression of miR-194-5p and a decrease in the expression of B-catenin, SOX5, p-STAT3 activated STAT3, VEGF, and MMP9 proteins was observed. Conclusions: According to the results of the present study, an increase in SOX2-OT in lung cancer seems to stimulate the expression of beta-catenin, SOX5, MMP9, and VEGF thus support the malignancy of lung cancer cells.