Down-regulation of IFITM1 and its growth inhibitory role in cervical squamous cell carcinoma

Weinan Zheng; Zhimin Zhao; Xinan Yi; Qiangqiang Zuo; Hongtao Li; Xiaoqing Guo; Dongmei Li; Hongchang He; Zemin Pan; Peiwen Fan; Feng Li; Yanhong Liao; Renfu Shao

doi:10.1186/s12935-017-0456-0

Down-regulation of IFITM1 and its growth inhibitory role in cervical squamous cell carcinoma

Cancer Cell Int. 2017 Oct 10:17:88. doi: 10.1186/s12935-017-0456-0. eCollection 2017.

Authors

Weinan Zheng^#^{1

2}, Zhimin Zhao^#^{1

2}, Xinan Yi³, Qiangqiang Zuo², Hongtao Li², Xiaoqing Guo², Dongmei Li², Hongchang He², Zemin Pan^{1

2

4}, Peiwen Fan², Feng Li², Yanhong Liao¹, Renfu Shao⁵

Affiliations

¹ 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.
² 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.
³ Department of Human Anatomy, Basic Medical Science Division, Hainan Medical University, Haikou, 571100 Hainan China.
⁴ Department of Biochemistry and Molecular Biology, School of Medicine, Shihezi University, Shihezi, China.
⁵ Genecology Research Centre, Centre for Animal Health Innovation, Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Maroochydore, DC, QLD 4558 Australia.

^# Contributed equally.

Abstract

Background: 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 IFITM1 gene in cervical squamous cell cancer is unclear.

Methods: To explore the role of IFITM1 in carcinogenesis of cervical cancer, we investigated the expression of IFITM1 gene in cervical squamous cell carcinoma. IFITM1 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 IFITM1 gene promoter was detected by methylation-specific PCR. We then transfected HeLa cells with IFITM1 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.

Results: The difference in IFITM1 protein expression between samples from chronic cervicitis and cervical carcinoma was statistically significant (P < 0.01). Ki-67 and PCNA protein expression levels were significantly higher in cervical cancer tissues than in their corresponding cervicitis tissues (P < 0.05 and P < 0.001, respectively). IFITM1 mRNA level was significantly lower in cervical cancer tissues than in normal cervical tissues (P < 0.05). Methylation of the IFITM1 gene promoter was significantly higher in cervical cancer than in normal cervical tissues (P < 0.05). Transfection of the IFITM1 pcDNA3.1 construct decreased cell migration and invasion of HeLa cells, inhibited cell proliferation, and increased cell apoptosis.

Conclusion: IFITM1 gene expression may reduce the proliferation, migration, and invasion of cervical squamous cancer cells.

Keywords: Cell proliferation; Cervical squamous cell carcinoma; IFITM1 gene; Migration and invasion.