Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
FEBS Open Bio. 2021 May;11(5):1504-1515. doi: 10.1002/2211-5463.13140. Epub 2021 Apr 3.
Lung adenocarcinoma (LUAD) is the primary epithelial tumor of the lung. The lack of clinical symptoms and specific molecular diagnostic indicators during the early stages of LUAD mean that the disease may not be detected until late stages, and the 5-year survival rate is only approximately 15%. Long non-coding RNA ALMS1 intronic script 1 (ALMS1-IT1) was previously reported to be correlated with the poor prognosis of head and neck squamous cell carcinoma patients. Here, we investigated whether ALMS1-IT1 has prognostic potential for LUAD. Bioinformatics analyses were performed to examine the expression and prognostic value of ALMS1 and AVL9 (for which gene expression is positively correlated with ALMS1-IT1 expression in LUAD) in LUAD based on TCGA and Oncomine databases. We report that ALMS1-IT1 and AVL9 were both highly expressed in LUAD and correlated with poor outcomes in LUAD patients. Of note, the prognosis of LUAD patients with low expression of both ALMS1-IT1 and AVL9 was superior to that of other patients. Furthermore, the proliferation, migration and invasion of LUAD cells were decreased in cells lacking ALMS1-IT1, and this decrease could be almost completely reversed through overexpression of AVL9. Gene set enrichment analysis revealed that expression of genes related to the cell cycle pathway is closely related to both the high expression of ALMS1-IT1 and AVL9 in LUAD. Finally, up-regulation of ALMS1-IT1 can activate the cyclin-dependent kinase pathway, whereas absence of AVL9 can reverse this activation, as shown by western blotting. In summary, ALMS1-IT1/AVL9 may promote the malignant progression of LUAD, at least in part by regulating the cyclin-dependent kinase pathway.
肺腺癌（LUAD）是肺部的主要上皮肿瘤。LUAD 在早期缺乏临床症状和特定的分子诊断指标，这意味着疾病可能直到晚期才被发现，5 年生存率仅约为 15%。长链非编码 RNA ALMS1 内含子转录本 1（ALMS1-IT1）先前被报道与头颈部鳞状细胞癌患者的不良预后相关。在这里，我们研究了 ALMS1-IT1 是否对 LUAD 具有预后潜力。我们基于 TCGA 和 Oncomine 数据库进行了生物信息学分析，以研究 ALMS1 和 AVL9（其基因表达与 LUAD 中的 ALMS1-IT1 表达呈正相关）在 LUAD 中的表达和预后价值。我们报告称，ALMS1-IT1 和 AVL9 在 LUAD 中均高表达，并与 LUAD 患者的不良预后相关。值得注意的是，ALMS1-IT1 和 AVL9 表达均低的 LUAD 患者的预后优于其他患者。此外，在缺乏 ALMS1-IT1 的 LUAD 细胞中，细胞增殖、迁移和侵袭能力降低，而通过过表达 AVL9 几乎可以完全逆转这种降低。基因集富集分析表明，与细胞周期途径相关的基因表达与 LUAD 中 ALMS1-IT1 和 AVL9 的高表达密切相关。最后，ALMS1-IT1 的上调可以激活细胞周期蛋白依赖性激酶途径，而 AVL9 的缺失可以逆转这种激活，如 Western blot 所示。总之，ALMS1-IT1/AVL9 可能通过调节细胞周期蛋白依赖性激酶途径促进 LUAD 的恶性进展。
