Department of Thyroid and Breast, Ningbo Medical Center Lihuili Eastern Hospital/Taipei Medical University Ningbo Medical Center, Ningbo, 315000, Zhejiang Province, China.
In Vitro Cell Dev Biol Anim. 2019 Aug;55(7):522-532. doi: 10.1007/s11626-019-00372-1. Epub 2019 Jul 1.
Emerging evidences exposed that long noncoding RNAs (lncRNAs) play important roles in various tumor progression including breast cancer (BC). However, the role of lncRNA ADP-dependent glucokinase antisense RNA 1 (ADPGK-AS1) in BC progression remains undiscovered. Hence, this study aimed to investigate the role of ADPGK-AS1 in BC. qRT-PCR was performed to investigate ADPGK-AS1 expression level in BC tissues and cell lines. The effect of ADPGK-AS1 knockdown on BC cellular process was assessed by loss-of-function assay. Luciferase reporter and RIP assay were performed to investigate the combination between ADPGK-AS1 and miR-3196. The combination between miR-3196 and orthodenticle homeobox 1 (OTX1) was verified by luciferase reporter assay. Finally, rescue assays were performed to confirm the effects of ADPGK-AS1/miR-3196/OTX1 axis on BC development. ADPGK-AS1 expression level was upregulated in BC tissues and cell lines. High expression of ADPGK-AS1 predicted poor prognosis for BC patients. Functionally, ADPGK-AS1 promoted cell proliferation, migration, induced epithelial-mesenchymal transition (EMT) process, and suppressed cell apoptosis. Mechanistically, ADPGK-AS1 acted as a miR-3196 sponge to release OTX1 in BC cells. Currently, ADPGK-AS1 acted as a competing endogenous RNA (ceRNA) via modulating miR-3196/OTX1 axis in BC.
越来越多的证据表明，长非编码 RNA（lncRNA）在包括乳腺癌（BC）在内的各种肿瘤进展中发挥着重要作用。然而，lncRNA ADP 依赖性葡萄糖激酶反义 RNA 1（ADPGK-AS1）在 BC 进展中的作用仍未被发现。因此，本研究旨在探讨 ADPGK-AS1 在 BC 中的作用。qRT-PCR 用于检测 BC 组织和细胞系中 ADPGK-AS1 的表达水平。通过功能丧失测定评估 ADPGK-AS1 敲低对 BC 细胞过程的影响。荧光素酶报告和 RIP 测定用于研究 ADPGK-AS1 和 miR-3196 之间的结合。通过荧光素酶报告测定验证 miR-3196 和同源异型盒 1（OTX1）之间的结合。最后，进行挽救实验以确认 ADPGK-AS1/miR-3196/OTX1 轴对 BC 发育的影响。ADPGK-AS1 在 BC 组织和细胞系中表达上调。ADPGK-AS1 的高表达预示着 BC 患者预后不良。功能上，ADPGK-AS1 促进细胞增殖、迁移，诱导上皮-间充质转化（EMT）过程，并抑制细胞凋亡。从机制上讲，ADPGK-AS1 在 BC 细胞中作为 miR-3196 的海绵来释放 OTX1。目前，ADPGK-AS1 通过调节 miR-3196/OTX1 轴在 BC 中作为竞争内源性 RNA（ceRNA）发挥作用。
