Background

Hypoxia-inducible lipid droplet-associated (HILPDA) is considered to have tumorigenic activity, but its function in lung adenocarcinoma (LUAD) is rarely known. This work aimed to assess the regulatory functions as well as the in-depth mechanism of HILPDA in LUAD.

Methods

The expression of HILPDA in LUAD tissues was analyzed based on TCGA database, and then qRT-PCR was performed to confirm the HILPDA expression in LUAD cell lines. Kaplan-Meier analysis was used to measure the correlation of HILPDA expression and overall survival in patients with LUAD. Then, Cell-Counting Kit-8 (CCK-8), colony formation and transwell assays were performed to detect cell proliferation, invasion and migration. Moreover, the pathways closely related to the high HILPDA expression was analyzed by Kyoto Encyclopedia of genes and Genomes (KEGG) analysis. The levels of Cell cycle pathway-related proteins were assessed using western blotting.

Results

Herein, we revealed that HILPDA was expressed at high levels in LUAD tissues and cell lines, and LUAD patients with the higher HILPDA expression presented the shorter survival time. Down-regulation of HILPDA in Calu-3 cells can retard cell proliferation, migration and invasion as well as arrest cells in the G1 phase, whereas overexpression of HILPDA in A549 cells presented a marked promotion on these phenotypes. Moreover, we surveyed that knockdown of HILPDA restrained the activation of cell cycle pathway, while up-regulation of HILPDA led to opponent outcomes.

Conclusions

In summing, HILPDA may act as an oncogenic factor in LUAD cells via modulating cell cycle pathway, which represent a novel biomarker of tumorigenesis in LUAD patients.

中文翻译：

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缺氧诱导的脂滴相关（HILPDA）通过调节细胞周期通路促进体外肺腺癌细胞的恶性表型

背景

缺氧诱导的脂滴相关 (HILPDA) 被认为具有致瘤活性，但其在肺腺癌 (LUAD) 中的功能鲜为人知。这项工作旨在评估 HILPDA 在 LUAD 中的调节功能和深入机制。

方法

基于TCGA数据库分析LUAD组织中HILPDA的表达，然后进行qRT-PCR以确认HILPDA在LUAD细胞系中的表达。Kaplan-Meier分析用于测量LUAD患者HILPDA表达与总生存的相关性。然后，进行细胞计数试剂盒-8 (CCK-8)、集落形成和 transwell 试验以检测细胞增殖、侵袭和迁移。此外，通过京都基因和基因组百科全书（KEGG）分析分析了与高 HILPDA 表达密切相关的途径。使用蛋白质印迹评估细胞周期通路相关蛋白的水平。

结果

在此，我们发现 HILPDA 在 LUAD 组织和细胞系中高水平表达，且 HILPDA 表达较高的 LUAD 患者生存时间较短。Calu-3 细胞中 HILPDA 的下调可以延缓细胞增殖、迁移和侵袭以及阻止细胞在 G1 期，而 HILPDA 在 A549 细胞中的过表达对这些表型有显着促进作用。此外，我们调查了 HILPDA 的敲低抑制了细胞周期途径的激活，而 HILPDA 的上调导致了对手的结果。

结论

总之，HILPDA 可能通过调节细胞周期通路在 LUAD 细胞中充当致癌因子，这代表了 LUAD 患者肿瘤发生的新生物标志物。