Recently, many emerging circular RNAs (circRNAs) have been studied in human malignancies, including gastric cancer (GC). Researches concerning cancers have revealed that aberrant expression of circRNAs play a big part in tumorigenesis and development of diverse malignant tumors. Although hsa_circ_0014130 (circPIP5K1A) has been confirmed to be closely related to non-small cell lung cancer (NSCLC) progression, the knowledge of its function on GC progression remains unclear. Therefore, it is of great interest to uncover the underlying role of circPIP5K1A in GC. The expression and characteristic of circPIP5K1A were separately analyzed by RT-qPCR, nucleic acid electrophoresis, RNase R and Actinomycin D treatment. CCK-8, colony formation, EdU, transwell, TUNEL, flow cytometry, luciferase reporter, RIP and RNA pull-down assays were employed to testify the regulatory role of circPIP5K1A in GC. In current study, circPIP5K1A, featured with closed-loop structure, was proved to be highly expressed in tissues and cells of GC. Loss-of-function assays depicted that silencing circPIP5K1A suppressed GC development. Follow-up mechanism tests unveiled that circPIP5K1A bound with miR-376c-3p and inhibition of miR-376c-3p reversed circPIP5K1A downregulation-mediated effect on GC progression. Additionally, ZNF146 was verified to be the downstream molecule of circPIP5K1A/miR-376c-3p axis in modulating GC progression. circPIP5K1A stimulates GC progression by sponging miR-376c-3p to upregulate ZNF146 expression.

中文翻译：

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CircPIP5K1A 通过 miR-376c-3p/ZNF146 轴促进胃癌进展

最近，许多新兴的环状 RNA (circRNA) 已在人类恶性肿瘤中进行了研究，包括胃癌 (GC)。有关癌症的研究表明，circRNAs的异常表达在多种恶性肿瘤的发生和发展中起重要作用。尽管 hsa_circ_0014130 (circPIP5K1A) 已被证实与非小细胞肺癌 (NSCLC) 进展密切相关，但其对 GC 进展的作用仍不清楚。因此，揭示circPIP5K1A在GC中的潜在作用具有重要意义。通过RT-qPCR、核酸电泳、RNase R和放线菌素D处理分别分析circPIP5K1A的表达和特征。CCK-8、集落形成、EdU、transwell、TUNEL、流式细胞仪、荧光素酶报告基因、采用 RIP 和 RNA pull-down 分析来证明 circPIP5K1A 在 GC 中的调节作用。在目前的研究中，circPIP5K1A具有闭环结构，被证明在GC组织和细胞中高表达。功能丧失分析表明沉默 circPIP5K1A 抑制了 GC 的发展。后续机制测试表明，circPIP5K1A 与 miR-376c-3p 结合，抑制 miR-376c-3p 可逆转 circPIP5K1A 下调介导的 GC 进展作用。此外，ZNF146 被证实是调节 GC 进展的 circPIP5K1A/miR-376c-3p 轴的下游分子。circPIP5K1A 通过海绵化 miR-376c-3p 上调 ZNF146 表达来刺激 GC 进展。被证明在GC的组织和细胞中高度表达。功能丧失分析表明沉默 circPIP5K1A 抑制了 GC 的发展。后续机制测试表明，circPIP5K1A 与 miR-376c-3p 结合，抑制 miR-376c-3p 可逆转 circPIP5K1A 下调介导的 GC 进展作用。此外，ZNF146 被证实是调节 GC 进展的 circPIP5K1A/miR-376c-3p 轴的下游分子。circPIP5K1A 通过海绵化 miR-376c-3p 上调 ZNF146 表达来刺激 GC 进展。被证明在GC的组织和细胞中高度表达。功能丧失分析表明沉默 circPIP5K1A 抑制了 GC 的发展。后续机制测试表明，circPIP5K1A 与 miR-376c-3p 结合，抑制 miR-376c-3p 可逆转 circPIP5K1A 下调介导的 GC 进展作用。此外，ZNF146 被证实是调节 GC 进展的 circPIP5K1A/miR-376c-3p 轴的下游分子。circPIP5K1A 通过海绵化 miR-376c-3p 上调 ZNF146 表达来刺激 GC 进展。ZNF146 被证实是调节 GC 进展的 circPIP5K1A/miR-376c-3p 轴的下游分子。circPIP5K1A 通过海绵化 miR-376c-3p 上调 ZNF146 表达来刺激 GC 进展。ZNF146 被证实是调节 GC 进展的 circPIP5K1A/miR-376c-3p 轴的下游分子。circPIP5K1A 通过海绵化 miR-376c-3p 上调 ZNF146 表达来刺激 GC 进展。