Long non-coding RNA DLGAP1-AS1 promotes the progression of gastric cancer via miR-515-5p/MARK4 axis

Long non-coding RNA (lncRNA) is an essential regulator of carcinogenesis and cancer progression. In the study, we explored the role of lncRNA DLGAP1-AS1 in gastric cancer (GC). qRT-PCR was carried out to detect DLGAP1-AS1 expression in GC tissues and cell lines. CCK-8 assay, EdU assay, and transwell experiments were employed to detect the malignant biological behaviors of GC cells with DLGAP1-AS1 knockdown or overexpression. Bioinformatics and dual-luciferase report assay were used to confirm the binding relationship between DLGAP1-AS1 and miR-515-5p. MARK4 expression was detected by western blot after DLGAP1-AS1/miR-515-5p was selectively regulated. DLGAP1-AS1 was up-regulated in GC tissues and cell lines, and its high expression was closely associated with larger tumor size, higher TNM stage, and lymph node metastasis. Furthermore, DLGAP1-AS1 overexpression enhanced cell proliferation, migration, and invasion, and miR-515-5p could reverse these effects. DLGAP1-AS1 participated in the regulation of the MARK4 signaling pathway by targeting miR-515-5p. DLGAP1-AS1 promoted GC progression through miR-515-5p/MARK4 signaling pathway.

长链非编码RNA（long non-coding RNA，lncRNA）是癌变与肿瘤进展的关键调控因子。本研究旨在探究长链非编码RNA DLGAP1-AS1在胃癌（gastric cancer，GC）中的生物学功能。采用实时荧光定量逆转录聚合酶链反应（quantitative real-time polymerase chain reaction，qRT-PCR）检测胃癌组织及细胞系中DLGAP1-AS1的表达水平；通过CCK-8实验、EdU掺入实验及Transwell实验，检测敲低或过表达DLGAP1-AS1后胃癌细胞的恶性生物学行为；借助生物信息学分析与双荧光素酶报告基因实验，验证DLGAP1-AS1与miR-515-5p的靶向结合关系；通过蛋白质印迹法（Western blot）检测选择性调控DLGAP1-AS1/miR-515-5p后微管亲和力调节激酶4（microtubule affinity-regulating kinase 4，MARK4）的表达水平。研究结果显示，DLGAP1-AS1在胃癌组织与细胞系中呈高表达状态，且其高表达与更大的肿瘤体积、更高的TNM分期及淋巴结转移密切相关。进一步研究表明，过表达DLGAP1-AS1可增强胃癌细胞的增殖、迁移与侵袭能力，而miR-515-5p能够逆转上述效应。DLGAP1-AS1通过靶向结合miR-515-5p参与调控MARK4信号通路，最终促进胃癌进展。