Department of General Surgery, The Affiliated Lihuili Hospital, Ningbo University(Ningbo Medical Center Lihuili Hospital), Ningbo 315100, Zhejiang, China.
Department of Healthcare Security and Price Management, The Affiliated Lihuili Hospital, Ningbo University (Ningbo Medical Center Lihuili Hospital), Ningbo 315100, Zhejiang, China.
Clinics (Sao Paulo). 2022 Jun 2;77:100047. doi: 10.1016/j.clinsp.2022.100047. eCollection 2022.
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.
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.
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.
LINC01857 promotes malignant phenotypes of PDAC cells via upregulation of SMOC2 by interacting with miR-19a-3p.
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。
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。
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。
LINC01857 通过与 miR-19a-3p 相互作用上调 SMOC2 促进 PDAC 细胞的恶性表型。
