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Dysregulation of SPRR3/miR-876-3p Axis Contributes to Tumorigenesis in Non-Small-Cell Lung Cancer

Authors Li Q, Wang Y, Hu R, Yang G

Received 9 January 2020

Accepted for publication 14 March 2020

Published 23 March 2020 Volume 2020:13 Pages 2411—2419

DOI https://doi.org/10.2147/OTT.S245422

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Sanjay Singh


Qin Li,1,* Yuxuan Wang,2,* Rongkuan Hu,3 Guang Yang1

1Department of Oncology, BenQ Medical Center, Nanjing Medical University, Nanjing 210029, People’s Republic of China; 2Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China; 3GenePharma Co., Ltd, Suzhou, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Rongkuan Hu 199 Dongping Street, Suzhou 215123, People’s Republic of China
Tel +86-512-86668828
Email rkhu@mail.ustc.edu.cn
Guang Yang 181 Zhuyuan Road, Suzhou 215010, People’s Republic of China
Tel +86-512-80838800
Email yangguang9002@163.com

Background: SPRR3, also known as esophagin, has been shown to be involved in the initiation and progression of numerous types of tumor. However, the biological function of SPRR3 that contributes to non-small-cell lung cancer (NSCLC) growth and migration is largely unknown.
Methods: The expression of SPRR3 and its association with EZH2 and miR-876-3p in NSCLC cells were determined by real-time PCR. Protein levels were measured by immunohistochemistry (IHC) and Western blot. Cell functions were studied by CCK-8, transwell assay, flow cytometry and dual-luciferase reporter assay. The effect of SPRR3 on tumor growth in vivo was evaluated in patient-derived xenograft (PDX) models.
Results: SPRR3 was up-regulated in most NSCLC cell lines and clinical tissues. Also, the correlation between SPRR3 expression and clinical features was significant. Functional studies confirmed that SPRR3 modulates cell proliferation, invasion and cell apoptosis in NSCLC via regulating EZH2, which is a well-known oncogene in NSCLC. Furthermore, SPRR3 was found to be a direct target of miR-876-3p that also plays a suppressor role in NSCLC.
Conclusion: These findings indicated that miR-876-3p/SPRR3/EZH2 signaling cascade exerts important roles in the regulation of NSCLC, suggesting that this pathway can serve as a potential therapeutic target in NSCLC.

Keywords: SPRR3, EZH2, miR-876-3p, NSCLC, tumorigenesis

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