Song Wei's research while affiliated with Wenzhou Medical University and other places

Background: Nasopharyngeal carcinoma (NPC) development involves many genetic alterations. This study profiled differentially expressed miRNAs and selected miR-375 for further study. Methods: Differentially expressed miRNAs (DE-miRNAs) were screened using online databases and subjected to various analyses. miR-375 mimics with negative control cDNA, and ubiquitin-specific protease 1 (USP1) as well as a vector-only control were transfected into NPC cells for analysis by quantitative PCR, western blotting, wound healing, Transwell, cell viability, flow cytometry, and luciferase gene reporter assays. Results: A total of 308 NPC and 23 normal tissues were analyzed, and 67 DE-miRNAs were identified. Among these, miR-375 was downregulated and miR-21-5p was upregulated. Bioinformatical analysis identified USP1 as a potential target gene of miR-375. Furthermore, miR-375 expression was decreased, whereas USP1 expression was increased in NPC. Increased USP1 expression was associated with poor survival of head and neck cancer patients. The luciferase assay confirmed miR-375 binding to the USP1 3'-untranslated region (UTR), while the transfection experiment confirmed miR-375 expression reduced USP1 expression, and USP1 overexpression reversed the anti-tumor activity of miR-375 in NPC cells, determined by tumor cell migration, invasion, apoptosis, and gene expression. In addition, USP1 overexpression activated phosphoinositide 3-kinase (PI3K) signaling, whereas a selective PI3K inhibitor (S2793) could reverse the effects of USP1 on NPC cells in vitro. Conclusions: This study confirmed decreased miR-375 expression and increased miR-21 expression in NPC tissues. Downregulated miR-375 expression led to USP1 upregulation, which in turn activated PI3K/Akt signaling and promoted NPC cell migration and invasion, but inhibited NPC cell apoptosis.

[This corrects the article DOI: 10.1155/2020/9704245.].

Purpose: In patients with nasopharyngeal carcinoma (NPC), the expression of PDK1 is remarkably improved in NPC tissue and correlated with the clinicopathological severity of NPC. We expressed miR-375 in NPC cells to study the effects on PDK1 gene expression. We also investigated the mechanism by which miR-375 affects the biological behavior of NPC cells through effects on PDK1. Methods: qRT-PCR was carried out to analyze miR-375 and PDK1 levels in NPC cells. NPC cells were transfected with miR-375 inhibitor or miR-375 mimic. CCK-8 testing, colony formation testing, transwell testing, and flow cytometry analysis were carried out to quantify the cells' biological behavior. Rescue experiments demonstrated that the recovery of PDK1 expression was able to reverse the influence of miR-375 inhibition on NPC diffusion and intrusion. The interaction between miR-375 and PDK1 was verified by dual-luciferase reporter gene testing. Results: The results revealed that miR-375 has a negative regulatory effect on PDK1 expression in NPC cells. Furthermore, PDK1 is a target gene for miR-375. The empirical results obtained demonstrated a negative correlation between tumor development and the level of miR-375 expression in NPC tissues. The excessive expression of miR-375 and the downregulation of PDK1 facilitated the diffusion and invasion of NPC cells. Conclusion: The diffusion and incursion of NPC cells may be inhibited by direct targeting of PDK1 and decreasing the expression of miR-375. Our study highlights efforts to target PDK1 and miR-375 as potential therapeutic strategies for use in the treatment of NPC.