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长链非编码 RNA DLGAP1-AS1 通过 miR-515-5p/MARK4 轴促进胃癌的进展。

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

机构信息

Department of Medical Oncology, Dongguan People's Hospital, Dongguan, Guangdong, China.

出版信息

Braz J Med Biol Res. 2021 May 24;54(8):e10062. doi: 10.1590/1414-431X2020e10062. eCollection 2021.

Abstract

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.

摘要

长链非编码 RNA(lncRNA)是癌发生和癌症进展的重要调节因子。在本研究中,我们探讨了 lncRNA DLGAP1-AS1 在胃癌(GC)中的作用。通过 qRT-PCR 检测 GC 组织和细胞系中 DLGAP1-AS1 的表达。通过 CCK-8 assay、EdU assay 和 transwell 实验检测 DLGAP1-AS1 敲低或过表达对 GC 细胞恶性生物学行为的影响。通过生物信息学和双荧光素酶报告实验证实 DLGAP1-AS1 与 miR-515-5p 的结合关系。选择性调节 DLGAP1-AS1/miR-515-5p 后,通过 Western blot 检测 MARK4 表达。在 GC 组织和细胞系中上调了 DLGAP1-AS1,其高表达与肿瘤体积较大、TNM 分期较高和淋巴结转移密切相关。此外,DLGAP1-AS1 过表达增强了细胞增殖、迁移和侵袭,而 miR-515-5p 可以逆转这些效应。DLGAP1-AS1 通过靶向 miR-515-5p 参与 MARK4 信号通路的调节。DLGAP1-AS1 通过 miR-515-5p/MARK4 信号通路促进 GC 进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b70/8148880/058aef6788ec/1414-431X-bjmbr-54-8-e10062-gf001.jpg

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