Introduction: FOXD2-AS1 is known to promote the development of several cancers. However, its role in pancreatic adenocarcinoma (PAAD) is unclear.Methods: Expression of FOXD2-AS1 and miR-30a-3p in PAAD patients was analyzed with RT-qPCR. A follow-up study was performed to analyze the prognostic value of FOXD2-AS1 for PAAD. Overexpression assays were performed to analyze the crosstalk between FOXD2-AS1 and miR-30a-3p. Cell invasion and migration were analyzed by transwell assays.Results: Analysis of the TCGA dataset revealed that FOXD2-AS1 was upregulated in PAAD tissues compared to the non-cancer tissues (1.89 vs. 0.2 TPM), indicating potential involvement of FOXD2-AS1 in PAAD. Our own data also showed FOXD2-AS1 was overexpressed in PAAD. Moreover, high FOXD2-AS1 levels predicted poor survival. It is predicted that miR-30a-3p can bind FOXD2-AS1, while their overexpression did not affect each other's expression. Correlation analysis revealed a significant correlation between FOXD2-AS1 and COX-2. In addition, FOXD2-AS1 overexpression increased COX-2 level, while miR-30a-3p played an opposite role. FOXD2-AS1 and COX-2 overexpression increased PAAD cell invasion and migration. MiR-30a-3p played an opposite role and inhibited the effects of FOXD2-AS1 and COX-2 overexpression. Conclusion:FOXD2-AS1 may promote PAAD cell invasion and migration by sponging miR-30a-3p to upregulate COX-2.
BACKGROUND: Non-small cell lung cancer (NSCLC) is the most commonly diagnosed solid tumor. Natural killer (NK) cell-based immunotherapy is a promising anti-tumor strategy in various cancers including NSCLC. OBJECTIVE: We aimed to investigate the specific mechanisms that regulate the killing effect of NK cells to NSCLC cells. METHODS: Reverse transcription-quantitative PCR (RT-qPCR) assay was applied to measure the levels of hsa-microRNA (miR)-301a-3p and Runt-related transcription factor 3 (RUNX3). Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of IFN-γ and TNF-α. Lactate dehydrogenase assay was applied to detect the killing effect of NK cells. Dualluciferase reporter assay and RNA immunoprecipitation (RIP) assay were carried out to confirm the regulatory relationship between hsa-miR-301a-3p and RUNX3. RESULTS: A low expression of hsa-miR-301a-3p was observed in NK cells stimulated by IL-2. The levels of IFN-γ and TNF-α were increased in NK cells of the IL-2 group. Overexpression of hsa-miR-301a-3p reduced the levels of IFN-γ and TNF-α as well as the killing effect of NK cells. Furthermore, RUNX3 was identified to be a target of hsamiR-301a-3p. hsa-miR-301a-3p suppressed the cytotoxicity of NK cells to NSCLC cells by inhibiting the expression of RUNX3. We found hsa-miR-301a-3p promoted tumor growth by suppressing the killing effect of NK cells against NSCLC cells in vivo. CONCLUSIONS: Hsa-miR-301a-3p suppressed the killing effect of NK cells on NSCLC cells by targeting RUNX3, which may provide promising strategies for NK cell-based antitumor therapies.
MicroRNAs (MiRNAs) are believed to significantly influence the occurrence and development of Non-small cell lung cancer (NSCLC). This study aims to clarify the action of hsa-miR-25-5p (miR-25) in NSCLC. Public datasets related to miR-25 expression from Gene Expression Omnibus (GEO) were retrieved. MiR-25 expression in the retrieved datasets were calculated using a fix-effects model (REM). Statistical analysis was performed using Stata 15.0, with standard mean difference (SMD) as the effect size. Downloaded from GEO database, two mRNA datasets, GSE18842 and GSE101929, was used to obtain differentially expressed genes (DEGs) using R 4.2.1 software. TargetScan and miRwalk 3.0 were used to predict hsa-miR-25-5p target genes. Subsequently, Gene Ontology (GO) enrichment analysis were conducted. We constructed protein–protein interaction (PPI) network using String and Cytoscape. The prognostic values of top 10 HUB genes were analyzed. Four datasets related to miR-25 expression were retrieved from GEO, including GSE27705, GSE29248, GSE63805 and GSE102286. The results of REM suggested that miR-25 expression was obviously increased in NSCLC versus adjacent noncancerous lung tissues (SMD = 0.06, 95% CI: 0.36–0.84, P <0.001). 244 DEGs associated with both NSCLC and hsa-miR-25-5p were identified. Numerous DEGs were significantly enriched in the locus of cell membranes, playing the roles of protein binding, and biological regulation. Based on PPI analysis, among the top 10 HUB genes, the high expressions of eight genes significantly reduced overall survival in NSCLC (CCNB1, RAD51AP1, MELK, NCAPH, MCM10, NUSAP, PRC1, BRCA). miR-25 displays an critical role in the biological process by binding target genes, influencing prognosis in patients with NSCLC.
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