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Abstract：
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.
摘要：
胆管癌(CCA)是一种高侵袭性、高死亡率的恶性肿瘤。大多数CCA案例在被检测到时已经提前了，导致预后不良。因此，目前仍需要鉴定CCA的有效生物标志物.据报道，长链非编码RNADLGAP1-AS2在神经胶质瘤和Wilms肿瘤中具有预后价值。这里,我们研究了DLGAP1-AS2在CCA中的功能。首先使用来自癌症基因组图谱数据库的数据,然后通过定量RT-PCR(qRT-PCR)在CCA细胞系中检查DLGAP1-AS2在CCA组织和正常组织中的差异表达。通过生物信息学分析对目标基因进行预测,并且使用荧光素酶测定法确认结合位点。DLGAP1-AS2在CCA中上调，和高DLGAP1-AS2表达促进细胞活力，并与不良预后相关。值得注意的是,DLGAP1-AS2充当抑制miR-505表达的海绵，miR-505降低CCA细胞中N-乙酰半乳糖胺转移酶10(GALNT10)的表达。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，与对照组相比，用si-DLGAP1-AS2和si-GALNT10共转染的细胞的恶性表型显着降低。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.
