SUMO4 small interfering RNA attenuates invasion and migration via the JAK2/STAT3 pathway in non‑small cell lung cancer cells

Liang,Jin-Xiao; Gao,Wei; Zeng,Xiao-Wei; Cheng,Guo-Ping; Cai,Lei; Tao,Kai-Yi; Yang,Xun

doi:10.3892/ol.2020.12088

SUMO4 small interfering RNA attenuates invasion and migration via the JAK2/STAT3 pathway in non‑small cell lung cancer cells

Authors:
- Jin-Xiao Liang
- Wei Gao
- Xiao-Wei Zeng
- Guo-Ping Cheng
- Lei Cai
- Kai-Yi Tao
- Xun Yang
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Affiliations: Department of Thoracic Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China, School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang 310000, P.R. China, Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310000, P.R. China
Published online on: September 11, 2020 https://doi.org/10.3892/ol.2020.12088
Article Number: 225
Copyright: © Liang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Small ubiquitin‑like modifier 4 (SUMO4) is the latest member of the sumoylation family, which enhances the stability of protein, regulates the distribution and localization of the protein, and affects the transcription activity of the protein. However, the role of SUMO4 in non‑small cell lung cancer (NSCLC) has not yet been reported. The present study first demonstrated that SUMO4 was upregulated in a number of tissues from patients with NSCLC. Immunohistochemistry was performed to demonstrate the expression level of SUMO4 in lung cancer tumor tissues. Following the transfection, The EMT status and signaling pathway activation regulated by SUMO4‑siRNA was assessed by western blotting. The Transwell and wound healing assays were performed to investigate the regulatory effect of SUMO4‑siRNA on cell migration and invasion. Cell Counting Kit‑8 assay was performed to investigate whether SUMO4‑siRNA affected the chemosensitivity of the NSCLC cells to cisplatin. Statistical analysis of immunohistochemical results from the tissues showed that the overexpression of SUMO4 was significantly associated with sex, tumor type, history of smoking, T stage and poor prognosis. It was also identified that SUMO4 small interfering RNA attenuated invasion and migration in NSCLC cell lines, as well chemosensitivity to cisplatin via the inhibition of the JAK2/STAT3 pathway. In conclusion, SUMO4 may play an important role in the poor prognosis of patients with NSCLC. The present study indicates that SUMO4 may be a potential therapeutic target for NSCLC.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI
2	Molina JR, Yang P, Cassivi SD, Schild SE and Adjei AA: Non-small cell lung cancer: Epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 83:584–594. 2008. View Article : Google Scholar : PubMed/NCBI
3	Pencik J, Pham HT, Schmoellerl J, Javaheri T, Schlederer M, Culig Z, Merkel O, Moriggl R, Grebien F and Kenner L: JAK-STAT signaling in cancer: From cytokines to non-coding genome. Cytokine. 87:26–36. 2016. View Article : Google Scholar : PubMed/NCBI
4	Yu Y, Zhao Q, Wang Z and Liu XY: Activated STAT3 correlates with prognosis of non-small cell lung cancer and indicates new anticancer strategies. Cancer Chemother Pharmacol. 75:917–922. 2015. View Article : Google Scholar : PubMed/NCBI
5	Song Q, Liu B, Li X, Zhang Q, Cao L, Xu M, Meng Z, Wu X and Xu K: MiR-26a-5p potentiates metastasis of human lung cancer cells by regulating ITGβ8- JAK2/STAT3 axis. Biochem Biophys Res Commun. 501:494–500. 2018. View Article : Google Scholar : PubMed/NCBI
6	Wilson VG: Introduction to sumoylation. Adv Exp Med Biol. 963:1–12. 2017. View Article : Google Scholar : PubMed/NCBI
7	Yang Y, He Y, Wang X, Liang Z, He G, Zhang P, Zhu H, Xu N and Liang S: Protein SUMOylation modification and its associations with disease. Open Biol. 7:1701672017. View Article : Google Scholar : PubMed/NCBI
8	Zhang J, Chen Z, Zhou Z, Yang P and Wang CY: Sumoylation modulates the susceptibility to type 1 diabetes. Adv Exp Med Biol. 963:299–322. 2017. View Article : Google Scholar : PubMed/NCBI
9	Li H, Yang Z, Pu LM, Li X, Ruan Y, Yang F, Meng S, Yang D, Yao W, Fu H, et al: Adiponectin receptor 1 and small ubiquitin-like modifier 4 polymorphisms are associated with risk of coronary artery disease without diabetes. J Geriatr Cardiol. 13:776–782. 2016.PubMed/NCBI
10	Alzolibani AA, Settin A, Ahmed AA, Ismail H, Elhefni N and Robaee AA: Genetic polymorphisms of NFκB1 −94 del/ins ATTG, NFκB1A 2758 A>G and SUMO rs237025 G>A in psoriasis. Int J Health Sci (Qassim). 9:25–33. 2015. View Article : Google Scholar : PubMed/NCBI
11	Hou S, Kijlstra A and Yang P: The genetics of behçet's disease in a Chinese population. Front Med. 6:354–359. 2012. View Article : Google Scholar : PubMed/NCBI
12	Chen S, Yang T, Liu F, Guo Y, Yang H, Xu J, Song J, Zhu Z and Liu D: Inflammatory factor-specific sumoylation regulates NF-κB signalling in glomerular cells from diabetic rats. Inflamm Res. 63:23–31. 2014. View Article : Google Scholar : PubMed/NCBI
13	Mo YY, Yu Y, Ee PL and Beck WT: Overexpression of a dominant negative mutant Ubc9 is associated with increased sensitivity to anticancer drugs. Cancer Res. 64:2793–2798. 2004. View Article : Google Scholar : PubMed/NCBI
14	Wang CY and She JX: SUMO4 and its role in type I diabetes pathogenesis. Diabetes Metab Res Rev. 24:93–102. 2008. View Article : Google Scholar : PubMed/NCBI
15	Shen QY, Wu HH, Liang JX, XU JY and Liang Y: Clinical significance of SUMO4 expression in papillary thyroid carcinoma. Chin J Pathophysiology. 31:1422–1426. 2015.
16	Sobin LH, Gospodarowicz MK and Wittekind C: TNM Classification of Malignant Tumours, International Union Against Cancer. 7th. A John Wiley & Sons, Ltd., Publication; 2009, http://www.inen.sld.pe/portal/documentos/pdf/educacion/13072015_TNM%20Classification.pdf
17	Gillett CE: Immunohistochemistry. Methods Mol Med. 120:191–200. 2006.PubMed/NCBI
18	Wilson VG and Rangasamy D: Incellular targeting of proteins by sumoylation. Exp Cell Res. 271:57–65. 2001. View Article : Google Scholar : PubMed/NCBI
19	Sarge KD and Park-Sarge OK: Sumo and its role in human diseases. Int Rev Cell Mol Biol. 288:167–183. 2011. View Article : Google Scholar : PubMed/NCBI
20	Huang HJ, Zhou LL, Fu WJ, Zhang CY, Jiang H, Du J and Hou J: β-Catenin SUMOylation is involved in the dysregulated proliferation of myeloma cells. Am J Cancer Res. 5:309–320. 2014.PubMed/NCBI
21	Bellail AC, Olson JJ and Hao C: SUMO1 modification stabilizes CDK6 protein and drives the cell cycle and glioblastoma progression. Nat Commun. 23:42342014. View Article : Google Scholar
22	Nestal de Moraes G, Ji Z, Fan LY, Yao S, Zona S, Sharrocks AD and Lam EW: SUMOylation modulates FOXK2-mediated paclitaxel sensitivity in breast cancer cells. Oncogenesis. 7:292018. View Article : Google Scholar : PubMed/NCBI
23	Guo D, Li M, Zhang Y, Yang P, Eckenrode S, Hopkins D, Zheng W, Purohit S, Podolsky RH, Muir A, et al: A functional variant of sumo4, a new i kappa b alpha modifier, is associated with type 1 diabetes. Nat Genet. 36:837–841. 2004. View Article : Google Scholar : PubMed/NCBI
24	Bohren KM, Nadkarni V, Song JH, Gabbay KH and Owerbach D: A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus. J Biol Chem. 279:27233–27238. 2004. View Article : Google Scholar : PubMed/NCBI