长链非编码 RNA LINC01857 通过调节 miR-19a-3p/SMOC2 驱动胰腺导管腺癌的进展。

OBJECTIVES: Emerging evidence has demonstrated that LINC01857 exerts a pivotal function in many cancers. However, its function in Pancreatic Ductal Adenocarcinoma (PDAC) still remains unclear. This study was designed to investigate the regulatory character of LINC01857 in PDAC. METHODS: Bioinformatic tools and databases were used to seek potential miRNAs and mRNAs. Gene expression was evaluated by Reverse Transcription quantitative real-time Polymerase Chain Reaction (RT-qPCR), and western blot was used for protein level detection. A subcellular fraction assay was done to ascertain the location of LINC01857 in PANC-1 and BxPC-3 human pancreatic cancer cells. CCK-8, EdU, wound healing and Transwell assays were performed to inquire into the influence of LINC01857, and SPARC -related Modular Calcium-binding protein-2 (SMOC2) on cell viability, proliferation, migration, and invasion, respectively. The interaction between LINC01857 and its downstream genes was explored by RNA immunoprecipitation and luciferase reporter assays. RESULTS: LINC01857 levels were significantly elevated in PDAC. Knockdown of LINC01857 significantly restrained the proliferation, migration, invasion, and Epithelial-Mesenchymal Transition (EMT) process of PDAC cells. MiR-19a-3p was a downstream target of LINC01857, and miR-19a-3p levels were significantly decreased in PDAC cells. In addition, SMOC2 expression had a negative correlation with that of miR-19a-3p, and SMOC2 was a downstream target of miR-19a-3p. Furthermore, SMOC2 upregulation partially abolished the inhibitive influence of LINC01857 downregulation on cell proliferation, migration, invasion, and the EMT process. CONCLUSION: LINC01857 promotes malignant phenotypes of PDAC cells via upregulation of SMOC2 by interacting with miR-19a-3p.

目的：新出现的证据表明 LINC01857 在许多癌症中发挥着关键作用。然而，其在胰腺导管腺癌（PDAC）中的功能仍不清楚。本研究旨在探讨 LINC01857 在 PDAC 中的调节作用。

方法：使用生物信息学工具和数据库寻找潜在的 miRNAs 和 mRNAs。通过逆转录定量实时聚合酶链反应（RT-qPCR）评估基因表达，并用 Western blot 检测蛋白水平。进行亚细胞分馏测定以确定 LINC01857 在 PANC-1 和 BxPC-3 人胰腺癌细胞中的位置。CCK-8、EdU、划痕愈合和 Transwell 测定分别用于研究 LINC01857 和 SPARC 相关模块化钙结合蛋白-2（SMOC2）对细胞活力、增殖、迁移和侵袭的影响。通过 RNA 免疫沉淀和荧光素酶报告基因测定探索 LINC01857 与其下游基因之间的相互作用。

结果：LINC01857 在 PDAC 中的水平显著升高。LINC01857 敲低显著抑制 PDAC 细胞的增殖、迁移、侵袭和上皮-间充质转化（EMT）过程。miR-19a-3p 是 LINC01857 的下游靶基因，并且在 PDAC 细胞中 miR-19a-3p 的水平显著降低。此外，SMOC2 的表达与 miR-19a-3p 的表达呈负相关，并且 SMOC2 是 miR-19a-3p 的下游靶基因。此外，SMOC2 的上调部分消除了 LINC01857 下调对细胞增殖、迁移、侵袭和 EMT 过程的抑制作用。

结论：LINC01857 通过与 miR-19a-3p 相互作用上调 SMOC2 促进 PDAC 细胞的恶性表型。