PDF(Pubmed)
Abstract：
Long non-coding RNAs (lncRNAs) play a crucial role in tumor generation and progression. However, the exact functional significance and underlying molecular mechanism by which lncRNA CERS6-AS1 operates in the context of lung adenocarcinoma (LUAD) remain unknown. We aimed to evaluate the potential role of the CERS6-AS1/miR-424-5p/ANLN axis in the progression of LUAD through bioinformatics and cytobehavioral experiments, and to provide a new insight into the combined treatment of LUAD. Based on the TCGA database, the expression of CERS6-AS1 in pan-cancer was evaluated, and its prognostic performance in LUAD was evaluated by ROC curve, survival curve and COX analysis. In addition, quantification of CERS6-AS1 expression levels in LUAD patients and lung cancer cells using quantitative real-time polymerase chain reaction (RT-qPCR), and further validate the functional significance of CERS6-AS1 in promoting the proliferation, migration, and invasion abilities of lung cancer cells. The competitive endogenous RNA (ceRNA) network was constructed, and miR-424-5p inhibitors were applied to CERS6-AS1 knockdown cells. The potential downstream genes associated with the regulatory axis of CERS6-AS1/miR-424-5p were analyzed by PPI network and gene enrichment analysis (KEGG). Finally, we evaluated the prognostic value of high expression of ANLN in LUAD and its effects on immune cell infiltration, tumor mutation burden, chemotherapy response, and immunotherapy. CERS6-AS1 expression was significantly elevated in both LUAD patients and lung cancer cells. In the CERS6-AS1 knockdown assay, the proliferation, invasion, migration and epithelial-mesenchymal transformation (EMT) of cancer cells were significantly inhibited. Notably, there was a prominent upregulation of miR-424-5p expression in cells where CERS6-AS1 was knocked down. Co-transfection of siRNA and miR-424-5p inhibitors into lung cancer cells restored the restriction on lung cancer cells. Anillin (ANLN) has been identified as a potential target gene for miR-424-5p and as a prognostic and immune biomarker associated with immune cell infiltration and tumor mutational burden in LUAD. Additionally, ANLN impacts the efficacy of chemotherapy and immunotherapy in LUAD patients. This study reveals a novel regulatory mechanism in which CERS6-AS1 may contribute to the progression of LUAD by influencing the expression of ANLN as a competitive sponge for miR-424-5p.
摘要：
长链非编码RNA（lncRNAs）在肿瘤的产生和进展中起着至关重要的作用。然而,lncRNACERS6-AS1在肺腺癌(LUAD)中的确切功能意义和潜在分子机制尚不清楚.我们旨在通过生物信息学和细胞行为实验评估CERS6-AS1/miR-424-5p/ANLN轴在LUAD进展中的潜在作用。并为LUAD的联合治疗提供新的见解。基于TCGA数据库,评估了CERS6-AS1在泛癌症中的表达，并通过ROC曲线评价其在LUAD中的预后表现，生存曲线和COX分析。此外,使用定量实时聚合酶链反应（RT-qPCR）定量LUAD患者和肺癌细胞中的CERS6-AS1表达水平，并进一步验证了CERS6-AS1在促进增殖中的功能意义，迁移,和肺癌细胞的侵袭能力。构建了竞争性内源RNA(ceRNA)网络,和miR-424-5p抑制剂应用于CERS6-AS1敲低细胞。通过PPI网络和基因富集分析（KEGG）分析与CERS6-AS1/miR-424-5p调控轴相关的潜在下游基因。最后,我们评估了ANLN在LUAD中高表达的预后价值及其对免疫细胞浸润的影响，肿瘤突变负荷，化疗反应，和免疫疗法。CERS6-AS1表达在LUAD患者和肺癌细胞中均显著升高。在CERS6-AS1敲低试验中,扩散,入侵,癌细胞的迁移和上皮间质转化（EMT）被显著抑制。值得注意的是,在CERS6-AS1下调的细胞中,miR-424-5p表达显著上调.siRNA和miR-424-5p抑制剂共转染到肺癌细胞中恢复了对肺癌细胞的限制。Anillin（ANLN）已被确定为miR-424-5p的潜在靶基因，并且是与LUAD中免疫细胞浸润和肿瘤突变负担相关的预后和免疫生物标志物。此外,ANLN影响LUAD患者化疗和免疫治疗的疗效。这项研究揭示了一种新的调节机制，其中CERS6-AS1可能通过影响ANLN作为miR-424-5p的竞争性海绵的表达来促进LUAD的进展。
