长非编码 RNA HAGLROS 通过抑制 miR-100 并上调 SMARCA5 促进 NSCLC 细胞的恶性表型。

BACKGROUND: Long non-coding RNA (lncRNA) is implicated in the progression of multiple cancers. This study aimed to explore the expression characteristics, biological function and molecular mechanism of lncRNA HAGLROS expression in NSCLC. METHODS: Quantitative real-time polymerase chain reaction (RT-PCR) was adopted to detect HAGLROS expression in NSCLC tissues and normal lung tissues. Survival curve was plotted by Kaplan-Meier method. Gain-of-function and loss-of-function models were respectively established to investigate the biological functions of HAGLROS, miR-100 and SMARCA5. MTT and Transwell assays were carried out to monitor the changes in proliferation, migration and invasion of NSCLC cells. Bioinformatics analysis and dual-luciferase reporter assay were used to verify the binding sites between HAGLROS and miR-100. Western blot was performed to determine the regulatory effects of HAGLROS and miR-100 on SMARCA5 protein expression. RESULTS: Up-regulated HAGLROS expression was observed in NSCLC tissues and cell lines. Over-expressed HAGLROS promoted the malignant phenotypes of NSCLC cells; conversely, HAGLROS knockdown repressed the malignant phenotypes of NSCLC cells. HAGLROS repressed miR-100 expression to promote SMARCA5 expression in NSCLC cells, and miR-100 overexpression or SMARCA5 knockdown counteracted the oncogenic functions of HAGLROS. CONCLUSIONS: These results conclude that HAGLROS is a tumor promoter in NSCLC, and it regulates the malignant phenotypes of NSCLC cells via miR-100/SMARCA5 axis.

背景：长链非编码 RNA（lncRNA）参与多种癌症的进展。本研究旨在探讨 lncRNA HAGLROS 在 NSCLC 中的表达特征、生物学功能和分子机制。

方法：采用实时定量聚合酶链反应（RT-PCR）检测 NSCLC 组织和正常肺组织中 HAGLROS 的表达。采用 Kaplan-Meier 法绘制生存曲线。分别建立 gain-of-function 和 loss-of-function 模型，研究 HAGLROS、miR-100 和 SMARCA5 的生物学功能。采用 MTT 和 Transwell 实验检测 NSCLC 细胞增殖、迁移和侵袭的变化。通过生物信息学分析和双荧光素酶报告基因实验验证 HAGLROS 与 miR-100 之间的结合位点。采用 Western blot 检测 HAGLROS 和 miR-100 对 SMARCA5 蛋白表达的调控作用。

结果：在 NSCLC 组织和细胞系中观察到上调的 HAGLROS 表达。过表达 HAGLROS 促进 NSCLC 细胞的恶性表型；相反，HAGLROS 敲低抑制 NSCLC 细胞的恶性表型。HAGLROS 抑制 miR-100 的表达，从而促进 NSCLC 细胞中 SMARCA5 的表达，而 miR-100 的过表达或 SMARCA5 的敲低则抵消了 HAGLROS 的致癌作用。

结论：这些结果表明，HAGLROS 是 NSCLC 的肿瘤促进因子，它通过 miR-100/SMARCA5 轴调节 NSCLC 细胞的恶性表型。