Department of Oncology, Thoracic, Head and Neck Surgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi, China.
Neoplasma. 2020 Jul;67(4):871-879. doi: 10.4149/neo_2020_190826N821. Epub 2020 May 6.
Non-small cell lung cancer (NSCLC) is a major source of cancer mortality. Long non-coding RNA DSCAM-AS1 has been certified to be involved in the pathogenesis of NSCLC. This study aimed to further investigate the potential mechanism of DSCAM-AS1 in NSCLC progression. The expressions of DSCAM-AS1, miR-577, and high mobility group box 1 (HMGB1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. Flow cytometry assay was conducted to monitor cell apoptosis. Cell migration and invasion were measured by transwell assay. Wnt/β-catenin pathway-related factors were detected by western blot assay. The relationship between DSCAM-AS1, miR-577, and HMGB1 was validated by bioinformatics analysis and dual-luciferase reporter assay. The xenograft mouse model was established to analyze tumor growth in vivo. DSCAM-AS1 and HMGB1 were upregulated, while miR-577 was downregulated in NSCLC tissues and cells. DSCAM-AS1 promoted cell proliferation, migration and invasion, and restrained cell apoptosis in NSCLC cells. Overexpression of HMGB1 reversed the effects of DSCAM-AS1 depletion on the progression of NSCLC. DSCAM-AS1 modulated HMGB1 expression by sponging miR-577. DSCAM-AS1 regulated the Wnt/β-catenin pathway by regulating miR-577 and HMGB1. DSCAM-AS1 knockdown blocked the tumor growth in vivo. In conclusion, DSCAM-AS1 facilitated NSCLC progression by regulating the HMGB1-mediated Wnt/β-catenin pathway, providing a promising therapeutic target for NSCLC.
非小细胞肺癌（NSCLC）是癌症死亡的主要原因。长链非编码 RNA DSCAM-AS1 已被证明参与 NSCLC 的发病机制。本研究旨在进一步探讨 DSCAM-AS1 在 NSCLC 进展中的潜在机制。通过实时定量聚合酶链反应（qRT-PCR）或 Western blot 检测 DSCAM-AS1、miR-577 和高迁移率族蛋白 1（HMGB1）的表达。通过细胞计数试剂盒-8（CCK-8）测定细胞活力。通过流式细胞术检测细胞凋亡。通过 Transwell 测定法检测细胞迁移和侵袭。通过 Western blot 检测 Wnt/β-catenin 通路相关因子。通过生物信息学分析和双荧光素酶报告基因检测验证 DSCAM-AS1、miR-577 和 HMGB1 之间的关系。通过建立异种移植小鼠模型分析体内肿瘤生长。在 NSCLC 组织和细胞中，DSCAM-AS1 和 HMGB1 上调，而 miR-577 下调。DSCAM-AS1 促进 NSCLC 细胞的增殖、迁移和侵袭，并抑制细胞凋亡。HMGB1 的过表达逆转了 DSCAM-AS1 耗竭对 NSCLC 进展的影响。DSCAM-AS1 通过海绵吸附 miR-577 调节 HMGB1 的表达。DSCAM-AS1 通过调节 miR-577 和 HMGB1 调节 Wnt/β-catenin 通路。DSCAM-AS1 敲低阻断了体内肿瘤的生长。总之，DSCAM-AS1 通过调节 HMGB1 介导的 Wnt/β-catenin 通路促进 NSCLC 的进展，为 NSCLC 提供了有前途的治疗靶点。
