OncoTargets and Therapy (Mar 2020)
Dysregulation of SPRR3/miR-876-3p Axis Contributes to Tumorigenesis in Non-Small-Cell Lung Cancer
Abstract
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 workCorrespondence: Rongkuan Hu 199 Dongping Street, Suzhou 215123, People’s Republic of ChinaTel +86-512-86668828Email [email protected] Yang 181 Zhuyuan Road, Suzhou 215010, People’s Republic of ChinaTel +86-512-80838800Email [email protected]: 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
