LncRNA DSCAM-AS1 promotes non-small cell lung cancer progression via regulating miR-577/HMGB1 axis

Zhang Qiu, Xi-Xiang Pan,  Dong-Yang You

Abstract:

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.