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microRNA-374a 通过靶向 SRCIN1 促进胰腺癌细胞增殖和上皮间质转化。

MicroRNA-374a promotes pancreatic cancer cell proliferation and epithelial to mesenchymal transition by targeting SRCIN1.

机构信息

Department of General Surgery, Tianjin Fifth Central Hospital, Tianjin, 300450, China.

Department of General Surgery, Tianjin Fifth Central Hospital, Tianjin, 300450, China.

出版信息

Pathol Res Pract. 2019 Jun;215(6):152382. doi: 10.1016/j.prp.2019.03.011. Epub 2019 Mar 5.

Abstract

MicroRNAs (miRNAs) play a vital role in the progress of cancer. Whereas the expression and function of miR-374a in pancreatic cancer remain largely unknown. In this study, pancreatic cancer samples and its adjacent normal tissues were obtained from 30 clinical patients with pancreatic cancer. Quantitative real-time PCR (qRT-PCR) was used to measure miR-374a and SRC Kinase Signaling Inhibitor 1 (SRCIN1) expression. Western blotting assay was performed to measure the levels of SRCIN1, E-cadherin, N-cadherin, Vimentin, Zonula occludens-1 (ZO-1) and β-catenin in PANC-1 cells. Luciferase reporter assay was conducted to confirm the direct targeting of SRCIN1 by miR-374a. Cell proliferation and migration assays were utilized to analyze the role of miR-374a in PANC-1 cells. We found that miR-374a expression was upregulated in pancreatic cancer tissues and cell lines. Over-expression of miR-374a promoted cell proliferation, migration and epithelial-mesenchymal transition (EMT) in pancreatic cancer. While, SRCIN1 expression was downregulated in pancreatic cancer tissues and cells. SRCIN1 was found to be a potential targets of miR-374a by dual-luciferase reporter assay. And SRCIN1 was down-regulated after miR-374a transfection. More than that, over-expression of SRCIN1 inhibited cell proliferation, migration and EMT in pancreatic cancer cell. Therefore, this study revealed that miR-374a promoted cell proliferation, migration and EMT via targeting SRCIN1 in pancreatic cancer.

摘要

微小 RNA(miRNAs)在癌症的进展中起着至关重要的作用。然而,miR-374a 在胰腺癌中的表达和功能仍知之甚少。在这项研究中,从 30 名胰腺癌患者中获得了胰腺癌样本及其相邻正常组织。采用定量实时 PCR(qRT-PCR)测量 miR-374a 和 SRC 激酶信号抑制剂 1(SRCIN1)的表达。通过 Western blot 测定 PANC-1 细胞中 SRCIN1、E-钙粘蛋白、N-钙粘蛋白、波形蛋白、紧密连接蛋白-1(ZO-1)和β-连环蛋白的水平。进行荧光素酶报告基因测定以确认 SRCIN1 是 miR-374a 的直接靶标。细胞增殖和迁移实验用于分析 miR-374a 在 PANC-1 细胞中的作用。我们发现 miR-374a 在胰腺癌组织和细胞系中表达上调。miR-374a 的过表达促进了胰腺癌中细胞的增殖、迁移和上皮-间充质转化(EMT)。然而,SRCIN1 在胰腺癌组织和细胞中表达下调。双荧光素酶报告基因测定发现 SRCIN1 是 miR-374a 的潜在靶标。并且转染 miR-374a 后 SRCIN1 下调。不仅如此,SRCIN1 的过表达抑制了胰腺癌细胞的增殖、迁移和 EMT。因此,本研究表明 miR-374a 通过靶向 SRCIN1 促进胰腺癌中细胞的增殖、迁移和 EMT。

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