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Long Noncoding RNA NEAT1 Upregulates Survivin and Facilitates Gallbladder Cancer Progression by Sponging microRNA-335

Authors Yang F, Tang Z, Duan A, Yi B, Shen N, Bo Z, Yin L, Zhu B, Qiu Y, Li J

Received 28 October 2019

Accepted for publication 13 February 2020

Published 20 March 2020 Volume 2020:13 Pages 2357—2367

DOI https://doi.org/10.2147/OTT.S236350

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Leo Jen-Liang Su


Facai Yang,1,* Zhaohui Tang,2,* Anqi Duan,3 Bin Yi,3 Ningjia Shen,3 Zhiyuan Bo,3 Lei Yin,3 Bin Zhu,3 Yinghe Qiu,3 Jingdong Li1

1Department of General Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, People’s Republic of China; 2Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, People’s Republic of China; 3Department of Biliary II, Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Military Medical University, Shanghai 200438, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yinghe Qiu
Department of Biliary II, Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Military Medical University, No. 225 Changhai Road, Yangpu District, Shanghai 200438, People’s Republic of China
Email qiuyinghe8@aliyun.com

Jingdong Li
Department of General Surgery, Affiliated Hospital of North Sichuan Medical College, No. 63, Wenhua Road, Shunqing District, Nanchong 637000, People’s Republic of China
Email lijingdong358@126.com

Background: Gallbladder cancer (GBC) is the most common cancer of the biliary tract, but molecularly targeted therapies are not available for GBC. Loss of microRNA (miR)-335 expression may be a useful predictor of clinical outcomes and the reversal of its loss of expression may be a useful treatment strategy for GBC. In this study, we investigated whether a long noncoding RNA, nuclear paraspeckle assembly transcript 1 (NEAT1) sponges miR-335 in GBC cells.
Materials and Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry were used to determine the expression of miR-335; NEAT1; survivin; and Ki67 in GBC cell lines (GBC-SD and SGC-996) and tissue samples from patients (n = 25). Cell Counting Kit-8, colony-formation, and Transwell migration and invasion assays were performed to measure cell proliferation, migration, and invasion. Bioinformatic analysis and dual-luciferase reporter assays were utilized to analyze correlativity.
Results: miR-335 overexpression resulted in inhibition of GBC cell proliferation and invasion. In addition, knockdown of NEAT1 resulted in downregulation of survivin expression. As NEAT1 competitively “sponges” miR-335, NEAT1 knockdown resulted in inhibited GBC cell proliferation and invasion in vitro and GBC tumor growth in vivo. Furthermore, NEAT1 was found to be upregulated in GBC samples, and its expression was inversely correlated with miR-335 levels, but positively correlated with survivin levels.
Conclusion: These findings indicate that NEAT1 promotes survivin expression by functioning as a competitive endogenous RNA for miR-335 in GBC cells; thus, we have identified a potential biomarker and target for GBC diagnosis and therapy.

Keywords: long noncoding RNA, NEAT1, miR-335-5p, competitive endogenous RNA, survivin, gallbladder cancer

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