Chen Xi, Guo Jishu, Zhou Fan, Ren Wenjun, Huang Xiaobin, Pu Jun, Niu Xiaoqun, Jiang Xiulin
Department of Neurosurgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.
Institute for Ecological Research and Pollution Control of Plateau Lakes, School of Ecology and Environmental Science, Yunnan University, Kunming, China.
Front Oncol. 2022 May 16;12:905871. doi: 10.3389/fonc.2022.905871. eCollection 2022.
Lung adenocarcinoma (LUAD) is the most common histological lung cancer, and it is the leading cause of cancer-related deaths worldwide. LncRNA-AL139385.1 (ENSG00000275880) is a novel lncRNA that is abnormally expressed in various cancer types including LUAD. However, the underlying biological function and potential mechanisms of AL139385.1 driving the progression of LUAD remain unclear. In this study, we investigated the role of AL139385.1 in LUAD and found that DNA hypomethylation was positively correlated with AL139385.1 expression in LUAD. Moreover, we uncover that the expression of AL139385.1 in LUAD tissues was significantly higher than that of AL139385.1 expression in adjacent normal tissues. Kaplan-Meier survival analysis showed that patients with higher AL139385.1 expression correlated with adverse overall survival and progression-free survival. Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) value of AL139385.1 was 0.808. Correlation analysis showed that AL139385.1 expression was associated with immune infiltration in LUAD. We also found that AL139385.1 was upregulated in LUAD cancer tissues and cell lines. Knockdown of AL139385.1 significantly inhibited cell proliferation and migration abilities of LUAD. Finally, we constructed a ceRNA network that includes hsa-miR-532-5p and four mRNAs (GALNT3, CYCS, EIF5A, and ITGB4) specific to AL139385.1 in LUAD. Subsequent Kaplan-Meier survival analysis suggested that polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3), cytochrome c, somatic (CYCS), eukaryotic translation initiation factor 5A (EIF5A), and integrin subunit beta 4 (ITGB4), were potential prognostic biomarkers for patients with LUAD. In conclusion, this finding provides possible mechanisms underlying the abnormal upregulation of AL139385.1 as well as a comprehensive view of the AL139385.1-mediated competing endogenous RNAs (ceRNA) network in LUAD, thereby highlighting its potential role in diagnosis and therapy.
肺腺癌（LUAD）是最常见的组织学类型肺癌，也是全球癌症相关死亡的主要原因。LncRNA-AL139385.1（ENSG00000275880）是一种新型lncRNA，在包括LUAD在内的多种癌症类型中异常表达。然而，AL139385.1驱动LUAD进展的潜在生物学功能和机制仍不清楚。在本研究中，我们调查了AL139385.1在LUAD中的作用，发现DNA低甲基化与LUAD中AL139385.1的表达呈正相关。此外，我们发现LUAD组织中AL139385.1的表达明显高于相邻正常组织中AL139385.1的表达。Kaplan-Meier生存分析表明，AL139385.1表达较高的患者总生存期和无进展生存期较差。受试者工作特征（ROC）曲线分析表明，AL139385.1的曲线下面积（AUC）值为0.808。相关性分析表明，AL139385.1的表达与LUAD中的免疫浸润有关。我们还发现AL139385.1在LUAD癌组织和细胞系中上调。敲低AL139385.1可显著抑制LUAD的细胞增殖和迁移能力。最后，我们构建了一个ceRNA网络，该网络包括hsa-miR-532-5p和LUAD中AL139385.1特有的四个mRNA（GALNT3、CYCS、EIF5A和ITGB4）。随后的Kaplan-Meier生存分析表明，多肽N-乙酰半乳糖胺基转移酶3（GALNT3）、细胞色素c体（CYCS）、真核翻译起始因子5A（EIF5A）和整合素亚基β4（ITGB4）是LUAD患者潜在的预后生物标志物。总之，这一发现提供了AL139385.1异常上调的潜在机制，以及LUAD中AL139385.1介导的竞争性内源性RNA（ceRNA）网络的全面视图，从而突出了其在诊断和治疗中的潜在作用。
