Department of General Surgery, the Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou, Jiangsu, 221002, PR China; Institute of Digestive Disease, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou, Jiangsu, 221002, PR China.
Department of General Surgery, the Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou, Jiangsu, 221002, PR China; Institute of Digestive Disease, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou, Jiangsu, 221002, PR China.
Biomed Pharmacother. 2020 Jun;126:109941. doi: 10.1016/j.biopha.2020.109941. Epub 2020 Mar 10.
Gastric cancer (GC) has been regarded as a kind of the most common cancers in gastrointestinal malignant tumors. Circular RNA (circRNA) is a newly discovered category of non-coding RNAs and plays a significant role in the initiation or development of human cancers. Nevertheless, the role of circPIP5K1A in GC remains unclear.
The relative expression level and the circular structure of circPIP5K1A were confirmedby RT-qPCR. The biological function of circPIP5K1A in GC was evaluated by colony formation, transwell and western blot assays. The binding capacity between miR-671-5p and circPIP5K1A (or KRT80) was assessed by luciferase reporter and Ago2-RIP assays. Protein levels of PI3K/AKT pathway were measured by western blot assay.
CircPIP5K1A was up-regulated in GC tissues and cells with a circular structure. Functionally, circPIP5K1A silence limited cell proliferation, invasion, migration and EMT process. Mechanistically, circPIP5K1A directly interacted with miR-671-5p to modulate KRT80 expression. Either miR-671-5p inhibitor or KRT80 overexpression could offset the inhibitory effect of circPIP5K1A depletion on GC development. Besides, circPIP5K1A played its oncogenic role in GC through regulating PI3K/AKT pathway. At last, circPIP5K1A promoted GC tumor growth in vivo.
CircPIP5K1A/miR-671-5p/KRT80 axis contributes to GC progression through PI3K/AKT pathway, implying this axis may be a potential therapeutic target for the treatment of GC patients.
胃癌（GC）一直被认为是胃肠道恶性肿瘤中最常见的癌症之一。环状 RNA（circRNA）是一种新发现的非编码 RNA 类别，在人类癌症的发生或发展中发挥着重要作用。然而，circPIP5K1A 在 GC 中的作用尚不清楚。
通过 RT-qPCR 证实 circPIP5K1A 的相对表达水平和环状结构。通过集落形成、transwell 和 Western blot 测定评估 circPIP5K1A 在 GC 中的生物学功能。通过荧光素酶报告和 Ago2-RIP 测定评估 miR-671-5p 与 circPIP5K1A（或 KRT80）之间的结合能力。通过 Western blot 测定测量 PI3K/AKT 通路的蛋白水平。
circPIP5K1A 在 GC 组织和细胞中呈上调表达，具有环状结构。功能上，circPIP5K1A 沉默限制了细胞增殖、侵袭、迁移和 EMT 过程。机制上，circPIP5K1A 直接与 miR-671-5p 相互作用，调节 KRT80 表达。miR-671-5p 抑制剂或 KRT80 过表达均可抵消 circPIP5K1A 耗竭对 GC 发展的抑制作用。此外，circPIP5K1A 通过调节 PI3K/AKT 通路在 GC 中发挥致癌作用。最后，circPIP5K1A 在体内促进 GC 肿瘤生长。
circPIP5K1A/miR-671-5p/KRT80 轴通过 PI3K/AKT 通路促进 GC 进展，表明该轴可能是治疗 GC 患者的潜在治疗靶点。
