Background Rapid proliferation and outgrowth of tumor cells frequently result in localized hypoxia, which has been implicated in the progression of lung cancer. The present study aimed to identify key long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) involved in hypoxia-induced A549 lung cancer cells, and to investigate their potential underlying mechanisms of action. Methods High-throughput sequencing was utilized to obtain the expression profiles of lncRNA and mRNA in both hypoxia-induced and normoxia A549 lung cancer cells. Subsequently, a bioinformatics analysis was conducted on the differentially expressed molecules, encompassing functional enrichment analysis, protein-protein interaction (PPI) network analysis, and competitive endogenous RNA (ceRNA) analysis. Finally, the alterations in the expression of key lncRNAs and mRNAs were validated using real-time quantitative PCR (qPCR). Results In the study, 1155 mRNAs and 215 lncRNAs were identified as differentially expressed between the hypoxia group and the normoxia group. Functional enrichment analysis revealed that the differentially expressed mRNAs were significantly enriched in various pathways, including the p53 signaling pathway, DNA replication, and the cell cycle. Additionally, key lncRNA-miRNA-mRNA relationships, such as RP11-58O9.2-hsa-miR-6749-3p-XRCC2 and SNAP25-AS1-hsa-miR-6749-3p-TENM4, were identified. Notably, the qPCR assay demonstrated that the expression of SNAP25-AS1, RP11-58O9.2, TENM4, and XRCC2 was downregulated in the hypoxia group compared to the normoxia group. Conversely, the expression of LINC01164, VLDLR-AS1, RP11-14I17.2, and CDKN1A was upregulated. Conclusion Our findings suggest a potential involvement of SNAP25-AS1, RP11-58O9.2, TENM4, XRCC2, LINC01164, VLDLR-AS1, RP11-14I17.2, and CDKN1A in the development of hypoxia-induced lung cancer. These key lncRNAs and mRNAs exert their functions through diverse mechanisms, including the competitive endogenous RNA (ceRNA) pathway.

中文翻译：

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鉴定缺氧诱导的 A549 肺癌细胞中关键的 lncRNA 和 mRNA，并通过高通量测序研究其潜在机制


背景肿瘤细胞的快速增殖和生长经常导致局部缺氧，这与肺癌的进展有关。本研究旨在鉴定参与缺氧诱导的 A549 肺癌细胞的关键长非编码 RNA (lncRNA) 和信使 RNA (mRNA)，并研究其潜在的潜在作用机制。方法采用高通量测序获得缺氧诱导和常氧诱导的A549肺癌细胞中lncRNA和mRNA的表达谱。随后，对差异表达分子进行生物信息学分析，包括功能富集分析、蛋白质相互作用（PPI）网络分析和竞争性内源RNA（ceRNA）分析。最后，使用实时定量 PCR (qPCR) 验证了关键 lncRNA 和 mRNA 表达的变化。结果 研究中，缺氧组和常氧组中有1155个mRNA和215个lncRNA被鉴定为差异表达。功能富集分析显示，差异表达的mRNA在多种通路中显着富集，包括p53信号通路、DNA复制和细胞周期。此外，还确定了关键的 lncRNA-miRNA-mRNA 关系，例如 RP11-58O9.2-hsa-miR-6749-3p-XRCC2 和 SNAP25-AS1-hsa-miR-6749-3p-TENM4。值得注意的是，qPCR 检测表明，与常氧组相比，缺氧组中 SNAP25-AS1、RP11-58O9.2、TENM4 和 XRCC2 的表达下调。相反，LINC01164、VLDLR-AS1、RP11-14I17.2 和 CDKN1A 的表达上调。结论 我们的研究结果表明 SNAP25-AS1、RP11-58O9.2、TENM4、XRCC2、LINC01164、VLDLR-AS1、RP11-14I17 可能参与其中。2、CDKN1A在缺氧诱发肺癌的发生发展中的作用。这些关键的 lncRNA 和 mRNA 通过不同的机制发挥其功能，包括竞争性内源 RNA (ceRNA) 途径。