Central Laboratory, Affiliated Traditional Chinese Hospital of Southwest Medical University, Luzhou, Sichuan, P. R. China.
Digest Department, Cent Hospital of Shanxian, Heze, Shandong, P. R. China.
PLoS One. 2021 Mar 4;16(3):e0247817. doi: 10.1371/journal.pone.0247817. eCollection 2021.
Pancreatic adenocarcinoma (PAAD) is a pancreatic disease with a high mortality rate in the world. This present research intends to identify the function of lncRNA LINC00857/miR-340-5p/Transforming growth factor alpha (TGFA) in the progression of PAAD.
Bioinformatics analysis was used to explore the differentially expressed lncRNA/miRNA/mRNA and analyze the relationship between lncRNA/miRNA/mRNA expression and prognosis of PAAD by enquiring TCGA, GEO and GTEX. KEGG pathway analysis and GO enrichment analysis were implemented to annotate the crucial genes regulated by LINC00857. The biological behaviors of PAAD cells were detected by CCK-8, colony formation and transwell assays. Interactive associations between LINC00857 and miR-340-5p, as well as miR-340-5p and TGFA were analyzed by dual luciferase assay.
By enquiring TCGA database, we got that LINC00857 was highly expressed in patients with PAAD and positively associated with worse prognosis in PAAD patients. Moreover, LINC00857 upregulation promoted the proliferation and clone formation abilities of PAAD cells. Afterwards, the downstream miRNA and mRNA targets of LINC00857 were picked up to construct a ceRNA network. Further study revealed that TGFA expression was positively regulated by LINC00857 and negatively regulated by miR-340-5p. Besides that, the inhibitory effect of miR-340-5p on PAAD cells growth and movement can be blocked by LINC00857 upregulation. While, the malignant behavior of PAAD cells induced by TGFA overexpression can be eliminated by LINC00857 knockdown.
Upregulation of LINC00857 improved growth, invasion and migration abilities of PAAD cells by modulation of miR-340-5p/TGFA, affording potential targets and biomarkers for the clinical diagnosis and treatment.
胰腺导管腺癌（PAAD）是一种死亡率很高的胰腺疾病。本研究旨在鉴定长链非编码 RNA LINC00857/miR-340-5p/转化生长因子α（TGFA）在 PAAD 进展中的作用。
使用生物信息学分析方法，通过查询 TCGA、GEO 和 GTEX 数据库，探讨差异表达的 lncRNA/miRNA/mRNA，并分析 lncRNA/miRNA/mRNA 表达与 PAAD 预后的关系。通过 KEGG 通路分析和 GO 富集分析，注释由 LINC00857 调控的关键基因。通过 CCK-8、集落形成和 Transwell 实验检测 PAAD 细胞的生物学行为。通过双荧光素酶报告实验分析 LINC00857 与 miR-340-5p 以及 miR-340-5p 与 TGFA 之间的相互作用关系。
通过查询 TCGA 数据库，我们发现 LINC00857 在 PAAD 患者中高表达，与 PAAD 患者的预后不良呈正相关。此外，LINC00857 的上调促进了 PAAD 细胞的增殖和克隆形成能力。随后，筛选出 LINC00857 的下游 miRNA 和 mRNA 靶标，构建 ceRNA 网络。进一步研究表明，TGFA 的表达受 LINC00857 正向调控，受 miR-340-5p 负向调控。此外，LINC00857 上调可阻断 miR-340-5p 对 PAAD 细胞生长和运动的抑制作用。而 TGFA 过表达诱导的 PAAD 细胞恶性行为可被 LINC00857 敲低消除。
上调 LINC00857 通过调节 miR-340-5p/TGFA 改善了 PAAD 细胞的生长、侵袭和迁移能力，为临床诊断和治疗提供了潜在的靶点和生物标志物。
