Cholangiocarcinoma (CCA) is a highly invasive malignant tumor with high mortality. Most cases of CCA are already advanced when they are detected, resulting in poor prognosis. As such, there is an ongoing need for the identification of effective biomarkers for CCA. The long noncoding RNA DLGAP1‐AS2 has been reported to have prognostic value in glioma and Wilms' tumor. Here, we investigated the function of DLGAP1‐AS2 in CCA. The differential expression of DLGAP1‐AS2 in CCA tissues and normal tissues was first examined using data from the The Cancer Genome Atlas database and then in CCA cell lines by quantitative RT‐PCR (qRT‐PCR). The target gene was predicted by bioinformatics analysis, and the binding sites were confirmed using luciferase assay. DLGAP1‐AS2 is up‐regulated in CCA, and high DLGAP1‐AS2 expression promotes cell viability and is associated with poor prognosis. Notably, DLGAP1‐AS2 acts as a sponge to suppress miR‐505 expression, and miR‐505 reduces the expression of N‐acetylgalactosaminyltransferase 10 (GALNT10) in CCA cells. Biofunctional experiments revealed that a miR‐505 inhibitor almost completely removed the inhibitory effect of si‐DLGAP1‐AS2 on CCA cell malignant progression, whereas the malignant phenotype of cells cotransfected with si‐DLGAP1‐AS2 and si‐GALNT10 was significantly reduced as compared with the control. In summary, the DLGAP1‐AS2/miR‐505/GALNT10 axis may contribute to regulating the malignant progression of CCA and may have potential as a novel target for CCA therapy.

中文翻译：

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长链非编码 RNA DLGAP1-AS2 通过 miR-505 和 GALNT10 促进胆管癌进展

胆管癌（CCA）是一种侵袭性很强的恶性肿瘤，死亡率很高。大多数CCA病例在被发现时已经晚期，导致预后不良。因此，一直需要鉴定 CCA 的有效生物标志物。据报道，长链非编码 RNA DLGAP1-AS2 在胶质瘤和肾母细胞瘤中具有预后价值。在这里，我们研究了 DLGAP1-AS2 在 CCA 中的功能。首先使用癌症基因组图谱数据库中的数据检查 DLGAP1-AS2 在 CCA 组织和正常组织中的差异表达，然后通过定量 RT-PCR (qRT-PCR) 在 CCA 细胞系中进行检查。通过生物信息学分析预测靶基因，并通过荧光素酶测定确认结合位点。DLGAP1-AS2 在 CCA 中上调，高 DLGAP1-AS2 表达促进细胞活力并与预后不良有关。值得注意的是，DLGAP1-AS2 作为海绵抑制 miR-505 的表达，而 miR-505 降低CCA 细胞中的N-乙酰半乳糖胺基转移酶 10 (GALNT10)。生物功能实验表明 miR-505 抑制剂几乎完全消除了 si-DLGAP1-AS2 对 CCA 细胞恶性进展的抑制作用，而与 si-DLGAP1-AS2 和 si-GALNT10 共转染的细胞的恶性表型显着降低。控制。总之，DLGAP1-AS2/miR-505/GALNT10 轴可能有助于调节 CCA 的恶性进展，并可能成为 CCA 治疗的新靶点。