The role of low density lipoprotein receptor-related protein 11 as a tumor promoter in cervical cancer
Authors Wang Y, Han S, You X, Shi X, Liu L, Sun Y, Ma Y, Qian Q, Liu H, Cui B, Zhang Y
Received 11 April 2019
Accepted for publication 20 August 2019
Published 30 August 2019 Volume 2019:11 Pages 8081—8093
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Nicola Ludin
Peer reviewer comments 2
Editor who approved publication: Professor Nakshatri
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 Zhang1
1Department 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 China
Correspondence: Youzhong Zhang
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, People’s Republic of China
*These authors contributed equally to this work
Background: 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
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