Department of Oncology and Hematology, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130012, P.R. China.
Mol Med Rep. 2018 Jul;18(1):1188-1196. doi: 10.3892/mmr.2018.9069. Epub 2018 May 23.
Studies have demonstrated that a number of microRNAs (miRNAs) are dysregulated in pancreatic ductal adenocarcinoma (PDAC), and alterations in their expression may affect the onset and progression of PDAC. Therefore, the expression patterns, biological functions and associated molecular mechanisms of miRNAs in PDAC should be elucidated for the development of novel therapeutic methods. Previous studies reported significant miRNA‑874 (miR‑874) dysregulation in multiple types of human cancer. However, the expression pattern, possible roles and underlying mechanisms of miR‑874 in PDAC remain to be elucidated. This study evaluated miR‑874 expression in PDAC and examined its biological functions and underlying mechanism of action in PDAC progression. miR‑874 expression was downregulated in PDAC tissues and cell lines. Functional experiments demonstrated that upregulation of miR‑874 inhibited cell proliferation and invasion in PDAC. Additionally, paired box 6 (PAX6) was predicted as a putative target of miR‑874 using bioinformatics analysis. Further experiments demonstrated that PAX6 may be the direct target gene of miR‑874 in PDAC. PAX6 knockdown exhibited similar inhibitory effects to miR‑874 overexpression in PDAC cells. In addition, restored PAX6 expression may reverse the suppressive roles of miR‑874 overexpression in PDAC cells. The results demonstrated that miR‑874 may serve tumor suppressive roles in PDAC by directly targeting PAX6. Therefore, miR‑874 may exhibit potential applications for treatment of patients with PDAC.
研究表明,许多 microRNAs(miRNAs)在胰腺导管腺癌(PDAC)中失调,其表达的改变可能会影响 PDAC 的发生和进展。因此,为了开发新的治疗方法,应该阐明 miRNA 在 PDAC 中的表达模式、生物学功能和相关分子机制。先前的研究报道了多种人类癌症中 miRNA-874(miR-874)的显著失调。然而,miR-874 在 PDAC 中的表达模式、可能的作用及其潜在机制仍有待阐明。本研究评估了 miR-874 在 PDAC 中的表达,并研究了其在 PDAC 进展中的生物学功能和潜在作用机制。miR-874 在 PDAC 组织和细胞系中表达下调。功能实验表明,miR-874 的上调抑制了 PDAC 中的细胞增殖和侵袭。此外,通过生物信息学分析预测配对盒 6(PAX6)是 miR-874 的潜在靶基因。进一步的实验表明,PAX6 可能是 miR-874 在 PDAC 中的直接靶基因。PAX6 敲低在 PDAC 细胞中表现出与 miR-874 过表达相似的抑制作用。此外,恢复 PAX6 的表达可能会逆转 miR-874 过表达对 PDAC 细胞的抑制作用。结果表明,miR-874 通过直接靶向 PAX6 在 PDAC 中发挥肿瘤抑制作用。因此,miR-874 可能在治疗 PDAC 患者方面具有潜在的应用价值。