Zheng Weinan, Zhao Zhimin, Yi Xinan, Zuo Qiangqiang, Li Hongtao, Guo Xiaoqing, Li Dongmei, He Hongchang, Pan Zemin, Fan Peiwen, Li Feng, Liao Yanhong, Shao Renfu
Department of Biochemistry and Molecular Biology, Department of Human Anatomy and Histology and Embryology, Basic Medical Science of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei China.
Department of Biochemistry and Molecular Biology, School of Medicine, Shihezi University, Xinjiang Endemic and Ethnic Disease and Education Ministry Key Laboratory, Shihezi, 832002 Xinjiang China.
Cancer Cell Int. 2017 Oct 10;17:88. doi: 10.1186/s12935-017-0456-0. eCollection 2017.
Cervical cancer is a major cause of death in women worldwide. Interferon-induced transmembrane protein 1 (IFITM1) is involved in antivirus defense, cell adhesion, and carcinogenesis in different tissues. However, the role of gene in cervical squamous cell cancer is unclear.
To explore the role of IFITM1 in carcinogenesis of cervical cancer, we investigated the expression of gene in cervical squamous cell carcinoma. mRNA level was measured by real-time quantitative RT-PCR in cervical cancer tissues and their adjacent normal tissues. IFITM1 protein level was measured by immunohistochemistry. Methylation in the gene promoter was detected by methylation-specific PCR. We then transfected HeLa cells with expression vector or control vector. IFITM1 expression was examined; cell migration and invasion were analyzed by wound healing assay and matrigel-coated transwell migration assays, respectively. HeLa cell proliferation was measured by cell counting kit-8 assay and cell cycle analysis. Cell apoptosis was analyzed by Annexin V/propidium iodide double staining assay.
The difference in IFITM1 protein expression between samples from chronic cervicitis and cervical carcinoma was statistically significant ( < 0.01). Ki-67 and PCNA protein expression levels were significantly higher in cervical cancer tissues than in their corresponding cervicitis tissues ( < 0.05 and < 0.001, respectively). mRNA level was significantly lower in cervical cancer tissues than in normal cervical tissues ( < ). Methylation of the gene promoter was significantly higher in cervical cancer than in normal cervical tissues ( < 0.05). Transfection of the pcDNA3.1 construct decreased cell migration and invasion of HeLa cells, inhibited cell proliferation, and increased cell apoptosis.
gene expression may reduce the proliferation, migration, and invasion of cervical squamous cancer cells.
宫颈癌是全球女性死亡的主要原因。干扰素诱导跨膜蛋白1(IFITM1)参与不同组织中的抗病毒防御、细胞黏附及致癌过程。然而,该基因在宫颈鳞状细胞癌中的作用尚不清楚。
为探究IFITM1在宫颈癌发生中的作用,我们检测了宫颈鳞状细胞癌中该基因的表达。通过实时定量逆转录聚合酶链反应(RT-PCR)检测宫颈癌组织及其相邻正常组织中IFITM1的mRNA水平。采用免疫组织化学法检测IFITM1蛋白水平。通过甲基化特异性PCR检测该基因启动子的甲基化情况。随后,我们用IFITM1表达载体或对照载体转染HeLa细胞。检测IFITM1表达;分别通过划痕实验和基质胶包被的Transwell迁移实验分析细胞迁移和侵袭能力。用细胞计数试剂盒-8实验及细胞周期分析检测HeLa细胞增殖情况。通过膜联蛋白V/碘化丙啶双染实验分析细胞凋亡情况。
慢性宫颈炎和宫颈癌样本中IFITM1蛋白表达差异具有统计学意义(P<0.01)。宫颈癌组织中Ki-67和增殖细胞核抗原(PCNA)蛋白表达水平显著高于相应宫颈炎组织(分别为P<0.05和P<0.001)。宫颈癌组织中IFITM1 mRNA水平显著低于正常宫颈组织(P<)。宫颈癌中该基因启动子的甲基化水平显著高于正常宫颈组织(P<0.05)。转染pcDNA3.1-IFITM1构建体可降低HeLa细胞迁移和侵袭能力,抑制细胞增殖,并增加细胞凋亡。
IFITM1基因表达可能降低宫颈鳞状癌细胞的增殖、迁移和侵袭能力。