BackgroundDespite being one of the most common benign tumors, the prevalence and pathogenesis of hemangiomas (HAs) are poorly understood. We aimed to identify the biological role of the long non-coding RNA (lncRNA) CASC9 in the HA-derived endothelial cell (HDECs) phenotype as well as elucidate the mechanism involved.MethodsThe expression of CASC9 was identified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). the effect of CASC9 on cell proliferation, migration and invasion of HDECs were examined by CCK8, wound healing, and transwell assay, respectively. Bioinformatics analysis and a luciferase reporter assay were utilized to investigated the mechanisms involved. The in vivo tumorigenesis capability of CASC9 on HA was also evaluated.ResultsThe expression of CASC9 was significantly elevated in HA tissue compared to normal tissue. Down-regulation of CASC9 inhibited proliferation, migration, and invasion of HDECs. The translation of cyclinD1, N-cadherin, Twist, and MMP2 was also decreased by CASC9 knockdown treatment. Furthermore, CASC9 over-expression exerted the opposite effect of proliferation, migration, and invasion of HDECs. We also found that CASC9 interacts with miR-125a-3p/Nrg1 to regulate cellular functions. Interestingly, miR-125a-3p can reverse the effect of CASC9 on proliferation, migration, and invasion of HDECs. Together, the clinical data showed that CASC9 expression is negatively correlated with miR-125a-3p expression and positively correlated with Nrg1 expression. CASC9 also exerted anti-tumorigenesis capability in vivo.ConclusionOur study indicates that CASC9 accelerates cell growth and invasion of HDECs and provides new insights for the diagnosis and molecular therapy of HA.

Background: The prognostic role of PD-L1 expression in surgically resected lung adenocarcinoma (ADC) remains controversial. The present study was aimed to clarify the role of PD-L1 expression in predicting prognosis and to investigate its biological function in ADC.Materials and Methods: The association between PD-L1 expression and clinical outcomes in patients with resected ADC was analyzed using immunohistochemistry (IHC) in our cohort (n=104), externally validated by a meta-analysis of 13 published studies. The biological role of PD-L1 in ADC was explored using gene set enrichment analysis (GSEA).Results: Positive PD-L1 expression in tumor cells was observed in 38.5% (40/104). High PD-L1 expression levels were significantly correlated with poor overall survival (P=0.008). Furthermore, the meta-analysis also showed that positive PD-L1 expression was associated with shorter OS than negative PD-L1 expression (HR= 1.75, 95% CI: 1.26-2.42; P<0.001). In subgroup analysis stratified according to ethnicity, the pooled results demonstrated that increased PD-L1 expression was an unfavorable prognostic factor for Asian populations (HR= 2.11, 95% CI: 1.48-3.02; P<0.001), but not for non-Asian populations (HR=1.16, 95% CI: 0.63-2.11, P=0.64). The pooled odds ratios (ORs) indicated that PD-L1 expression was associated with positive lymph node metastasis (OR=1.74, 95% CI: 1.23-2.46; P=0.002) and male (OR=1.56, 95% CI: 1.02-2.37; P=0.04). GSEA revealed PD-L1 expression levels positively correlated with immune process or immune-related pathways.Conclusion: PD-L1 expression is an important negative prognostic factor in resected ADC. This finding has important implications for immunotherapy targeting the PD-1/PD-L1 pathway in patients with resected ADC.

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