The role of low density lipoprotein receptor-related protein 11 as a tumor promoter in cervical cancer

Ying Wang,1,2,* Sai Han,1,* Xuewu You,1 Xuejiao Shi,3 Lu Liu,1 Yu Sun,1 Yana Ma,1 Qiuhong Qian,1 Hongli Liu,1 Baoxia Cui,1 Youzhong Zhang11Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, People’s Republic of China; 2Department of Obstetrics and Gynecology, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, People’s Republic of China; 3Department of Rheumatism and Immunology, Weihai Municipal Hospital, Weihai, Shandong 264200, People’s Republic of ChinaCorrespondence: Youzhong ZhangDepartment of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, People’s Republic of ChinaEmail zhangyouzhong@sdu.edu.cn*These authors contributed equally to this workBackground: It is unclear whether low density lipoprotein receptor-related protein 11 (LRP11), a newly found lipoprotein receptor regulatory protein, has the carcinogenic effects in cervical cancer.Methods: Bioinformatics analysis, immunohistochemical (IHC) staining and evaluation, cell proliferation assay, flow cytometry, transwell migration and invasion assays, Western blotting, growth of LRP11-silenced cells in athymic nude mice were performed in this research.Results: We found that LRP11 expression was higher in high-grade squamous intraepithelial lesions (HSIL) and cervical cancer tissue than in normal cervix, and high expression of LRP11 was associated with differentiation degree (P=0.0266), indicating poor prognosis (P=0.0210). The silencing of LRP11 in SiHa and CaSki cell lines inhibited cell proliferation, reduced migration and invasion and suppressed cell growth in nude mice, which possibly related to cell cycle protein regulation of CDK 2/4, cyclin D1/E1, MMP-2/9, and VEGF. Furthermore, LRP11 showed substantial positive correlation with P16 in vivo and in vitro.Conclusion: LRP11 plays important roles in proliferation, migration and invasion, with the potential to be a useful prognostic marker and therapeutic target for patients with HSIL and cervical cancer.Keywords: HPV, cervical cancer, LRP11, P16, cell cycle