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lncRNA WT1-AS inhibits the aggressiveness of cervical cancer cell via regulating p53 expression via sponging miR-330-5p

Authors Cui LJ, Nai MM, Zhang K, Li L, Li RM

Received 6 June 2018

Accepted for publication 27 September 2018

Published 11 January 2019 Volume 2019:11 Pages 651—667

DOI https://doi.org/10.2147/CMAR.S176525

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Professor Nakshatri


LiJuan Cui,1,* ManMan Nai,2,* Ke Zhang,1 Lu Li,3 RuiMin Li4

1Department of Gynecology, First People’s Hospital of Jiaozuo City, Jiaozuo, Henan Province, China; 2Department of Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China; 3Department of Gynecology, Second People’s Hospital of Jiaozuo City, Jiaozuo, Henan Province, China; 4Department of Gynecology, Jiaozuo Maternal and Child Care Service Center, Jiaozuo, Henan Province, China

*These authors contributed equally to this work

Background: Emerging evidences have demonstrated that lncRNAs play vital roles in various pathological processes, including cancer. The lncRNA WT1 antisense RNA (WT1-AS) serves as a tumor suppressor in various cancers. Nevertheless, the expression and precise function of WT1-AS in cervical carcinoma still remain not yet investigated. The objective of our study was to explore the expression of WT1-AS and its biological roles in cervical cancer.
Methods: Differences in the lncRNA expression profiles between cervical cancer and adjacent normal tissues were assessed by lncRNA expression microarray analysis. The expression of p53 in cervical cancer cell was assessed by qRT-PCR and immunofluorescence assay. Loss-of-function studies were used to explore the effect of lncRNA WT1-AS on the growth and metastasis of cervical cancer cell in vitro and in vivo.
Results: Our results demonstrated that WT1-AS was remarkably down-regulated in cervical carcinoma. Functional assays proved that up-regulation of WT1-AS significantly suppressed cervical cancer cell proliferation, migration and invasion. In addition, the luciferase reporter assay identified that miR-330-5p was the target of WT1-AS. Moreover, tumor suppressor p53 was identified as the direct target of miR-330-5p and alternation of miR-330-5p/p53 axis reversed the effects of WT1-AS in cervical cancer cell.
Conclusion: Altogether, our findings suggested that WT1-AS was down-regulated in cervical carcinoma and WT1-AS suppressed cervical carcinoma cell- proliferation, migration and invasion through regulating the miR-330-5p/p53 axis.

Keywords: cervical cancer, WT1-AS, miR-330-5p, p53, metastasis

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