Preeclampsia (PE), a common obstetrical disorder, is characterized by impaired migration and invasion abilities of trophoblastic cells. MicroRNA-183-5p (miR-183) was reported to regulate cell migration and invasion in various types of human cancers; however, its role in the pathogenesis of PE remains elusive. Herein, we investigated the role of miR-183 in HTR-8/SVneo trophoblast cells invasion and migration and explored the underlying mechanism. Our results showed that miR-183 was significantly up-regulated in placental tissues from pregnant women compared with that in normal pregnant women. Overexpression of miR-183 inhibited proliferation, migration and invasion, as well as induced apoptosis in HTR-8/SVneo cells. Otherwise, down-regulation of miR-183 achieved the opposite effects. Bioinformatics prediction and luciferase reporter assay confirmed that matrix metalloproteinase-9 (MMP-9) is a target of miR-183. In addition, MMP-9 expression was significantly down-regulated, and inversely correlated with the miR-183 level in placental tissues from pregnant women with severe PE. Down-regulation of MMP-9 suppressed the trophoblast cell invasion and migration, whereas overexpression of MMP-9 promoted cell invasion and migration in HTR-8/SVneo cells. More importantly, up-regulation of MMP-9 reversed the inhibitory effects of miR-183 on cell invasion and migration in trophoblast cells. Collectively, our findings suggested that miR-183 may play critical roles in the pathogenesis of PE and serve as a potential biomarker for severe PE.
ObjectiveA review argues that polo-like kinase 5 (PLK5) may be linked to unfavorable prognosis in non-small cell lung cancer (NSCLC) patients, which contradicts the discoveries from The Human Protein Atlas database (derived from TCGA analysis). This study intended to comprehensively confirm the association of PLK5 with clinical characteristics and prognosis in NSCLC patients.MethodsThis two-center, retrospective, cohort study enrolled 210 NSCLC patients receiving surgical resection. PLK5 protein and mRNA were detected by immunohistochemistry and RT-qPCR in tumor and nontumor tissues. Moreover, RNA FPKM data for 994 lung cancer patients were obtained from The Human Protein Atlas database.ResultsPLK5 protein was decreased in tumor tissue compared to nontumor tissue (P < 0.001). Additionally, decreased PLK5 protein was linked with increased pathological grade (P = 0.002), lymph node metastasis presence (P = 0.001), elevated tumor-node-metastasis (TNM) stage (P = 0.003), and abnormal cancer antigen 125 (CA125) (P = 0.002). Meanwhile, low PLK5 protein was correlated with shortened disease-free survival (DFS) (P = 0.007) and overall survival (OS) (P = 0.038); further multivariable Cox regression analysis revealed that low PLK5 protein independently predicted unfavorable DFS (hazard ratio = 0.573, P = 0.022). PLK5 mRNA was reduced in tumor tissue compared with nontumor tissue (P < 0.001); its decline was linked with enhanced pathological grade (P = 0.034), climbed TNM stage (P = 0.032), and abnormal CA125 (P = 0.002). Furthermore, low PLK5 mRNA was correlated with unfavorable DFS (P = 0.046). The Human Protein Atlas database also disclosed the link between low PLK5 mRNA and worse OS (P = 0.046).ConclusionA PLK5 decrement reflects anabatic tumor burden and poor prognosis in NSCLC patients.
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