Abstract

While the application of early screening and HPV vaccines has reduced the incidence and mortality rates of cervical cancer, it remains the third most common carcinoma and fourth leading cause of cancer-associated death among women worldwide. The precise mechanisms underlying progression of cervical cancer are not fully understood at present. Here, we detected significant down-regulation of 15-hydroxyprostaglandin dehydrogenase (HPGD) in cervical cancer tissues. Overexpression of HPGD inhibited cervical cancer cell proliferation, migration and anchorage-independent growth to a significant extent. To clarify the mechanisms underlying HPGD down-regulation in cervical cancer, miRNA microarray, bioinformatics and luciferase reporter analyses were performed. HPGD was identified as a direct target of miR-146b-3p displaying up-regulation in cervical cancer tissues. Similar to the effects of HPGD overexpression, down-regulation of miR-146b-3p strongly suppressed proliferation, migration and anchorage-independent growth of cervical cancer cells. Furthermore, HPGD negatively regulated activities of STAT3 and AKT that promote cervical cancer cell proliferation. Notably, HPV oncogenes E6 and E7 were determined as potential contributory factors to these alterations. Our results collectively suggest that the HPGD/miR-146b-3p axis plays a significant role in cervical cancer and may serve as a potentially effective therapeutic target.

Details

Title
Down-regulation of HPGD by miR-146b-3p promotes cervical cancer cell proliferation, migration and anchorage-independent growth through activation of STAT3 and AKT pathways
Author
Yao, Shuihong 1 ; Xu, Jingyun 2 ; Zhao, Kaixuan 2 ; Song, Pengxia 3 ; Yan, Qin 4 ; Fan, Weifei 5 ; Li, Wan 4 ; Lu, Chun 4 

 Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing, P. R. China (GRID:grid.89957.3a) (ISNI:0000 0000 9255 8984); Quzhou College of Technology, Medical School, Quzhou, P. R. China (GRID:grid.469581.7) (ISNI:0000 0004 1776 2538) 
 Nanjing Medical University, Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing, P. R. China (GRID:grid.89957.3a) (ISNI:0000 0000 9255 8984); Nanjing Medical University, Department of Microbiology, Nanjing, P. R. China (GRID:grid.89957.3a) (ISNI:0000 0000 9255 8984) 
 Quzhou College of Technology, Medical School, Quzhou, P. R. China (GRID:grid.469581.7) (ISNI:0000 0004 1776 2538) 
 Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing, P. R. China (GRID:grid.89957.3a) (ISNI:0000 0000 9255 8984); Nanjing Medical University, Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing, P. R. China (GRID:grid.89957.3a) (ISNI:0000 0000 9255 8984); Nanjing Medical University, Department of Microbiology, Nanjing, P. R. China (GRID:grid.89957.3a) (ISNI:0000 0000 9255 8984) 
 Geriatric Hospital of Nanjing Medical University, Department of Hematology and Oncology, Department of Geriatric Lung Cancer Research Laboratory, Nanjing, P. R. China (GRID:grid.89957.3a) (ISNI:0000 0000 9255 8984) 
Pages
1055
Publication year
2018
Publication date
Nov 2018
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2830003765
Copyright
© The Author(s) 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.