Background Cervical cancer (CC) is one of the most common gynecological malignancies all around the world. The mechanisms of cervical carcinoma formation remain under close scrutiny. The long non-coding RNAs (lncRNA) and microRNAs (miRNAs) play important roles in controlling gene expression and promoting the development and progression of cervical cancer by acting as competitive endogenous RNA (ceRNA). However, the roles of lncRNA associated with ceRNAs in cervical carcinogenesis remains unknown. In this study, the expression of LncRNA HOTAIR was investigated in HPV16 positive cervical cancer cells, the candidate miRNAs and target genes were identified to clarify putative ceRNAs of HOTAIR/miRNA in cervical cancer cells. Methods The proliferate ability of cells was measured by CCK8 and EdU incorporation assays and cell apoptosis was analyzed by flow cytometry. The expression of HOTAIR, miR-214-3p, HPV16 E7 mRNA were detected by qRT-PCR. As for searching for the interaction between miR-214-3p and HOTAIR, the binding sites for miR-214-3p on HOTAIR was predicted by starbase v2.0 database, then dual-luciferase assay was used to verify the binding sites. In addition, Gene Ontology (GO) and protein-protein interaction (PPI) network analysis of target genes of miR-214-3p were performed with bioinformatics analysis. For potential signaling pathway regulated by miR-214-3p, we conducted pathway enrichment analysis by KEGG analysis and obtained key pathways in cervical cancer cells. Results Our results showed that the expression of HOTAIR was up-regulated, while that of miR-214-3p was down-regulated in HPV16-positive cervical cancer cells. The expression status of HPV16 E7 played an important role in regulating the expression of HOTAIR or miR-214-3p in cervical cancer cells. LncRNA HOTAIR knockdown could significantly inhibited cell proliferate ability and promote cellular apoptosis, whereas the inhibition of miR-214-3p expression partially reversed such results. Bioinformatics analysis identified 1451 genes as target genes of miR-214-3p. The Gene ontology (GO) and KEGG Pathway enrichment analysis showed that these target genes were mainly related to regulation of cell communication, protein binding, enzyme binding and transferase activity, and Wnt ligand biogenesis. Pathway enrichment analysis results showed that the predicted target genes were significantly enriched in Wnt/β-catenin signaling pathway. Finally, our results confirmed that miR-214-3p could significantly inhibit β-catenin expression in HPV16 positive cancer cells by qPCR and WB analysis. Conclusion HOTAIR could act as a ceRNA through binding to miR-214-3p, promote cell proliferation and inhibit the apoptosis of HPV16 positive cervical cancer. HOTAIR/miR-214-3p/Wnt/β-catenin signaling pathway might play important roles related with HPV16 positive cervical cancer. Our results provided a new perspective for identifying novel biomarkers for cervical cancer.

Background：Lung adenocarcinoma (LUAD) is the main histological subtype of lung cancer. However, the molecular mechanism underlying LUAD is not yet clearly defined, but elucidating this process in detail would be of great significance for clinical diagnosis and treatment. Our aim is to identify the candidate key genes and pathways associated with diagnosis and prognosis in LUAD.Methods：In this study, three gene expression profiles GSE118370, GSE32863 and GSE43458 were retrieved from Gene Expression Omnibus database (GEO), and the common differentially expressed genes (DEGs) were identified by online GEO2R analysis tool. Subsequently, the enrichment analysis of function and signaling pathways of DEGs in LUAD were performed by gene ontology (GO) and The Kyoto Encyclopedia of Genes and Genomics (KEGG) analysis. The protein-protein interaction (PPI) networks of the DEGs were established through the Search Tool for the Retrieval of Interacting Genes (STRING) database and hub genes were screened by plug-in CytoHubba in Cytoscape. Afterwards, the miRNAs and the hub genes network was constructed via miRWalk. Finally, receiver operating characteristic (ROC) curve and Kaplan-Meier plotter were performed to analyze the diagnosis and prognosis efficacy of hub genes. Results: A total of 311 DEGs were identified, including 74 up-regulated and 238 down-regulated genes. GO analysis results showed that DEGs were mainly enriched in biological processes including composition of extracellular matrix, regulation of angiogenesis and so on. KEGG analysis results revealed DEGs were mainly enrolled in cell adhesion signaling pathway. Subsequently, 10 hub genes, CDC20, CENPF, TPX2, TOP2A, KIAA0101, CDCA7, ASPM, ECT2, UBE2T and COL1A1, were identified. And TOP2A, CDCA7, TPX2 and COL1A1 showed strong relationships with each other and the miRNAs nearby in miRNAs-mRNA network obtained by miRWalk website. Finally, all these 10 hub genes were found significantly related to the diagnosis and prognosis of LUAD (p<0.05). Conclusions: The identification of hub genes in this study will help us to understand the pathogenesis of LUAD, especially the molecular mechanisms of its development. Our results suggested that TOP2A, CDCA7, TPX2 and COL1A1 might present predictive value for the development and prognosis in LUAD, and might be used as potential molecular markers for the diagnosis and treatment of LUAD.