Department of Dermatology, Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, China.
Eur Rev Med Pharmacol Sci. 2019 Apr;23(7):2888-2897. doi: 10.26355/eurrev_201904_17567.
Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are playing critical roles in tumorigenesis. The present study aimed to investigate the expression pattern and effects of lncRNA DSCAM-AS1 (DSCAM-AS1) that was a newly discovered lncRNA in melanoma.
Real-time quantitative PCR (polymerase chain reaction) was performed to determine the expression of DSCAM-AS1 in melanoma tissues and cell lines. Kaplan-Meier and Cox regression analyses were utilized to assess the association between the DSCAM-AS1 and overall survival of patients in melanoma patients. The CCK-8 assay, colony formation assay, flow cytometry assays, transwell and wound scratch assays were performed to determine the biological function of DSCAM-AS1 in tumor cells behaviors. Then, DSCAM-AS1-specific miRNA was further confirmed using the dual-luciferase reporter assay and Western blotting.
In this research, we showed that the expression of DSCAM-AS1 was significantly upregulated in melanoma samples and cell lines. Clinical investigation indicated that higher expression of DSCAM-AS1 was associated with ulceration and advanced stage and led to significantly poorer survival time. High DSCAM-AS1 expression in melanoma was confirmed to be an independent predictor of poor survival of patients using univariate and multivariate analysis. Functional investigations revealed that knockdown of DSCAM-AS1 inhibited the ability of cell proliferation, colony formation, migration, invasion, whereas promoted cell apoptosis. Furthermore, mechanistic investigations indicated that DSCAM-AS1 could interact with miR-136 and negatively influence the expression of miR-136.
Our findings showed that DSCAM-AS1 is a novel tumor-related molecule involved in melanoma progression as well as a potential prognostic biomarker and therapeutic target.
越来越多的证据表明，长链非编码 RNA（lncRNA）在肿瘤发生中发挥着关键作用。本研究旨在探讨新发现的 lncRNA DSCAM-AS1（DSCAM-AS1）在黑色素瘤中的表达模式和作用。
实时定量聚合酶链反应（PCR）用于确定黑色素瘤组织和细胞系中 DSCAM-AS1 的表达。Kaplan-Meier 和 Cox 回归分析用于评估 DSCAM-AS1 与黑色素瘤患者总生存率之间的关联。CCK-8 测定、集落形成测定、流式细胞术测定、transwell 和划痕实验用于确定 DSCAM-AS1 在肿瘤细胞行为中的生物学功能。然后，使用双荧光素酶报告基因测定和 Western blot 进一步证实 DSCAM-AS1 的特异性 miRNA。
在这项研究中，我们表明 DSCAM-AS1 的表达在黑色素瘤样本和细胞系中显著上调。临床研究表明，DSCAM-AS1 表达较高与溃疡和晚期有关，导致生存时间显著缩短。使用单因素和多因素分析证实，黑色素瘤中高 DSCAM-AS1 表达是患者生存不良的独立预测因子。功能研究表明，DSCAM-AS1 敲低抑制了细胞增殖、集落形成、迁移和侵袭能力，而促进了细胞凋亡。此外，机制研究表明，DSCAM-AS1 可以与 miR-136 相互作用，负调控 miR-136 的表达。
我们的研究结果表明，DSCAM-AS1 是一种新的肿瘤相关分子，参与黑色素瘤的进展，是一个潜在的预后生物标志物和治疗靶点。
