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 Obste...

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Main Authors: Wang Y, Han S, You X, Shi X, Liu L, Sun Y, Ma Y, Qian Q, Liu H, Cui B, Zhang Y
Format: Article
Language:English
Published: Dove Medical Press 2019-08-01
Series:Cancer Management and Research
Subjects:
Online Access:https://www.dovepress.com/the-role-of-low-density-lipoprotein-receptor-related-protein-11-as-a-t-peer-reviewed-article-CMAR
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author Wang Y
Han S
You X
Shi X
Liu L
Sun Y
Ma Y
Qian Q
Liu H
Cui B
Zhang Y
author_facet Wang Y
Han S
You X
Shi X
Liu L
Sun Y
Ma Y
Qian Q
Liu H
Cui B
Zhang Y
author_sort Wang Y
collection DOAJ
description 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
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spelling doaj.art-9fd6020c3f2041edae3d6a9170c04bb72022-12-22T02:38:04ZengDove Medical PressCancer Management and Research1179-13222019-08-01Volume 118081809348246The role of low density lipoprotein receptor-related protein 11 as a tumor promoter in cervical cancerWang YHan SYou XShi XLiu LSun YMa YQian QLiu HCui BZhang YYing 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 cyclehttps://www.dovepress.com/the-role-of-low-density-lipoprotein-receptor-related-protein-11-as-a-t-peer-reviewed-article-CMARHPVcervical cancerLRP11P16cell cycle
spellingShingle Wang Y
Han S
You X
Shi X
Liu L
Sun Y
Ma Y
Qian Q
Liu H
Cui B
Zhang Y
The role of low density lipoprotein receptor-related protein 11 as a tumor promoter in cervical cancer
Cancer Management and Research
HPV
cervical cancer
LRP11
P16
cell cycle
title The role of low density lipoprotein receptor-related protein 11 as a tumor promoter in cervical cancer
title_full The role of low density lipoprotein receptor-related protein 11 as a tumor promoter in cervical cancer
title_fullStr The role of low density lipoprotein receptor-related protein 11 as a tumor promoter in cervical cancer
title_full_unstemmed The role of low density lipoprotein receptor-related protein 11 as a tumor promoter in cervical cancer
title_short The role of low density lipoprotein receptor-related protein 11 as a tumor promoter in cervical cancer
title_sort role of low density lipoprotein receptor related protein 11 as a tumor promoter in cervical cancer
topic HPV
cervical cancer
LRP11
P16
cell cycle
url https://www.dovepress.com/the-role-of-low-density-lipoprotein-receptor-related-protein-11-as-a-t-peer-reviewed-article-CMAR
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