Zhang Lei, Wang Zhenyong, Kong Deshuai, Zhao Xiulei, Chen Xiongfei, Chai Wei
First Department of General Surgery, Cangzhou Central Hospital , Cangzhou, Hebei, China.
Biosci Biotechnol Biochem. 2020 Aug;84(8):1603-1613. doi: 10.1080/09168451.2020.1762479. Epub 2020 May 20.
Pancreatic cancer (PC), highly malignant, is one of the most lethal cancers. Interferon-induced transmembrane protein 1 (IFITM1) has recently been regarded as a new molecular marker in human cancers. However, the role of IFITM1 in PC remains unclear. In this study, a short hairpin RNA (shRNA) was constructed to assess the effect of IFITM1 on PANC-1 and ASPC-1 cells. The level of IFITM1 was downregulated in cells transfected with shRNA targeting IFITM1 (sh-IFITM1). Silencing of IFITM1 significantly decreased cell viability, downregulated the level of Ki-67, arrested cell at G1/S phase, reduced the number of cells in S phase, and decreased cyclinD1, cyclinE, CDK2, and CDK4 levels. Moreover, Hoechst staining and Western blotting analysis showed that cell apoptosis was induced by IFITM1. IFITM1 knockdown suppressed the MAPK signaling pathway by downregulation of p-ERK, p-P38, and p-JNK levels. These findings suggested that IFITM1 could be considered a potential therapeutic target for PC.
胰腺癌（PC）具有高度恶性，是最致命的癌症之一。干扰素诱导跨膜蛋白1（IFITM1）最近被视为人类癌症中的一种新分子标志物。然而，IFITM1在胰腺癌中的作用仍不清楚。在本研究中，构建了短发夹RNA（shRNA）以评估IFITM1对PANC-1和ASPC-1细胞的影响。在转染靶向IFITM1的shRNA（sh-IFITM1）的细胞中，IFITM1水平下调。IFITM1的沉默显著降低细胞活力，下调Ki-67水平，使细胞停滞在G1/S期，减少S期细胞数量，并降低细胞周期蛋白D1、细胞周期蛋白E、细胞周期蛋白依赖性激酶2（CDK2）和细胞周期蛋白依赖性激酶4（CDK4）水平。此外，Hoechst染色和蛋白质印迹分析表明，IFITM1可诱导细胞凋亡。IFITM1基因敲低通过下调p-ERK、p-P38和p-JNK水平抑制丝裂原活化蛋白激酶（MAPK）信号通路。这些发现表明，IFITM1可被视为胰腺癌的潜在治疗靶点。
