Inhibition of SNCG suppresses the proliferation of lung cancer cells induced by high glucose

Fei,Jing; Xiao,Chi; Yang,Meiying; Zhou,Xue; Gong,Ping

doi:10.3892/mmr.2020.11777

Inhibition of SNCG suppresses the proliferation of lung cancer cells induced by high glucose

Authors:
- Jing Fei
- Chi Xiao
- Meiying Yang
- Xue Zhou
- Ping Gong
View Affiliations

Affiliations: Department of Oncology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang 832000, P.R. China, Department of Clinical Medicine, Shihezi University School of Medicine, Shihezi, Xinjiang 832000, P.R. China
Published online on: December 13, 2020 https://doi.org/10.3892/mmr.2020.11777
Article Number: 138
Copyright: © Fei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Lung cancer is the most common cancer type worldwide and the leading cause of cancer-related mortality. Diabetes is closely associated with the occurrence, development and prognosis of lung cancer. Therefore, the present study aimed to investigate whether SNCG could affect the proliferation of lung cancer cells induced by high glucose. Lung cancer cells induced by high glucose simulated the pathologies of patients with lung cancer with diabetes in vitro. The proliferation of HBE cells and lung cancer cells after transfection and treatment of glucose was detected using Cell Counting Kit-8 assay. The mRNA expression levels of synuclein γ (SNCG), insulin-like growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1R) in HBE cells and lung cancer cells alone, or cells induced by high glucose were analyzed via reverse transcription-quantitative (RT-q)PCR analysis. Moreover RT-qPCR analysis was used to determine the transfection efficiencies. The clone formation ability, migration and inflammation of lung cancer cells after high glucose induction and transfection were detected using clone formation, wound healing and ELISA assays. The protein expression levels of SNCG, IGF-1, IGF-1R, ERK 1/2, phosphorylated (p)-ERK1/2 and JNK in lung cancer cells after high glucose induction and transfection were determined using western blot analysis. The results suggested that high glucose significantly promoted the proliferation of A549, NCI-H1975 and SK-MES-1 cells at 24 and 48 h, as well as upregulated the expression levels of SNCG, IGF-1 and IGF-1R. Knockdown of SNCG suppressed the proliferation, clone formation ability and migration, but alleviated inflammation in A549 cells induced by high glucose. Knockdown of SNCG suppressed the expression levels of SNCG, IGF-1, IGF-1R, ERK1/2 and p-ERK1/2, while it promoted JNK expression in A549 cells induced by high glucose. The effect of AXL1717 (an IGF-1R inhibitor) treatment on cells was consistent with that of SNCG knockdown. In conclusion, inhibition of SNCG suppresses proliferation of lung cancer cells induced by high glucose.

View Figures

View References

1	Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, Gaudet MM, Jemal A and Siegel RL: Ovarian cancer statistics, 2018. CA Cancer J Clin. 68:284–296. 2018. View Article : Google Scholar : PubMed/NCBI
2	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI
3	Edwards BK, Brown ML, Wingo PA, Howe HL, Ward E, Ries LA, Schrag D, Jamison PM, Jemal A, Wu XC, et al: Annual report to the nation on the status of cancer, 1975–2002, featuring population-based trends in cancer treatment. J Natl Cancer Inst. 97:1407–1427. 2005. View Article : Google Scholar : PubMed/NCBI
4	Han C, Zhang M, Luo X, Wang C, Yin L, Pang C, Feng T, Ren Y, Wang B, Zhang L, et al: Secular trends in the prevalence of type 2 diabetes in adults in China from 1995 to 2014: A meta-analysis. J Diabetes. 9:450–461. 2017. View Article : Google Scholar : PubMed/NCBI
5	Sona MF, Myung SK, Park K and Jargalsaikhan G: Type 1 diabetes mellitus and risk of cancer: A meta-analysis of observational studies. Jpn J Clin Oncol. 48:426–433. 2018. View Article : Google Scholar : PubMed/NCBI
6	Luo J, Chen YJ and Chang LJ: Fasting blood glucose level and prognosis in non-small cell lung cancer (NSCLC) patients. Lung Cancer. 76:242–247. 2012. View Article : Google Scholar : PubMed/NCBI
7	Yu WS, Lee CY, Park SY, Suh JW, Narm KS, Kim DJ, Chung KY and Lee JG: Prognostic factors for resected non-small cell lung cancer in patients with type 2 diabetes mellitus. J Surg Oncol. 117:985–993. 2018. View Article : Google Scholar : PubMed/NCBI
8	Ji H, Liu YE, Jia T, Wang M, Liu J, Xiao G, Joseph BK, Rosen C and Shi YE: Identification of a breast cancer-specific gene, BCSG1, by direct differential cDNA sequencing. Cancer Res. 57:759–764. 1997.PubMed/NCBI
9	Bruening W, Giasson BI, Klein-Szanto AJP, Lee VM, Trojanowski JQ and Godwin AK: Synucleins are expressed in the majority of breast and ovarian carcinomas and in preneoplastic lesions of the ovary. Cancer. 88:2154–2163. 2000. View Article : Google Scholar : PubMed/NCBI
10	Gu YM, Tan JX, Lu XW, Ding Y, Han X and Sun YJ: BCSG1 methylation status and BCSG1 expression in breast tissues derived from Chinese women with breast cancer. Oncology. 74:61–68. 2008. View Article : Google Scholar : PubMed/NCBI
11	Tastekin D, Kargin S, Karabulut M, Yaldız N, Tambas M, Gurdal N, Tatli AM, Arslan D, Gok AF and Aykan F: Synuclein-gamma predicts poor clinical outcome in esophageal cancer patients. Tumour Biol. 35:11871–11877. 2014. View Article : Google Scholar : PubMed/NCBI
12	Ye Q, Wang TF, Peng YF, Xie J, Feng B, Qiu MY, Li LH, Lu AG, Liu BY and Zheng MH: Expression of α-, β- and γ-synuclein in colorectal cancer, and potential clinical significance in progression of the disease. Oncol Rep. 23:429–436. 2010.PubMed/NCBI
13	Liu C, Shi B, Hao C, Wang Q, Lv Q, Xing N, Shou J, Qu L, Gao Y, Qin C, et al: Urine gamma-synuclein as a biomarker for the diagnosis of bladder cancer. Oncotarget. 7:43432–43441. 2016. View Article : Google Scholar : PubMed/NCBI
14	Zheng Y, Jiang J, Zhao N, Liu R, Yang C, Zhang J, Sun M and Zhang X: Expression of γ-synuclein in non-small cell lung cancer. Zhongguo Laonianxue Zazhi. 31:4771–4773. 2011.
15	Li M, Yin Y, Hua H, Sun X, Luo T, Wang J and Jiang Y: The reciprocal regulation of γ-synuclein and IGF-I receptor expression creates a circuit that modulates IGF-I signaling. J Biol Chem. 285:30480–30488. 2010. View Article : Google Scholar : PubMed/NCBI
16	Higashi Y, Sukhanov S, Anwar A, Shai SY and Delafontaine P: Aging, atherosclerosis, and IGF-1. J Gerontol A Biol Sci Med Sci. 67:626–639. 2012. View Article : Google Scholar : PubMed/NCBI
17	Xu C: Insulin-like growth factor type 1 receptor and malignancy:An update. Journal of Modern Oncology. 23:706–709. 2015.
18	Annibalini G, Lucertini F, Agostini D, Vallorani L, Gioacchini A, Barbieri E, Guescini M, Casadei L, Passalia A, Del Sal M, et al: Concurrent aerobic and resistance training has anti-inflammatory effects and increases both plasma and leukocyte levels of IGF-1 in late middle-aged type 2 diabetic patients. Oxid Med Cell Longev. 2017:39378422017. View Article : Google Scholar : PubMed/NCBI
19	Pollak M: The insulin and insulin-like growth factor receptor family in neoplasia: An update. Nat Rev Cancer. 12:159–169. 2012. View Article : Google Scholar : PubMed/NCBI
20	Ding CZ, Guo XF, Wang GL, Wang HT, Xu GH, Liu YY, Wu ZJ, Chen YH, Wang J and Wang WG: High glucose contributes to the proliferation and migration of non-small cell lung cancer cells via GAS5-TRIB3 axis. Biosci Rep. 38:BSR201710142018. View Article : Google Scholar
21	Zhang J, Luo W, Chi X, Zhang L, Ren Q, Wang H and Zhang W: IGF2BP1 silencing inhibits proliferation and induces apoptosis of high glucose-induced non-small cell lung cancer cells by regulating Netrin-1. Arch Biochem Biophys. 693:1085812020. View Article : Google Scholar : PubMed/NCBI
22	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
23	Hemminki K, Li X, Sundquist J and Sundquist K: Risk of cancer following hospitalization for type 2 diabetes. Oncologist. 15:548–555. 2010. View Article : Google Scholar : PubMed/NCBI
24	Cheng X and Han Y: Impact of diabetes mellitus on lung cancer and its biological mechanism: A Literature Review. Chin Gen Pract. 21:1779–1784. 2018.
25	Luo J, Hendryx M, Qi L, Ho GY and Margolis KL: Pre-existing diabetes and lung cancer prognosis. Br J Cancer. 115:76–79. 2016. View Article : Google Scholar : PubMed/NCBI
26	Zhu L, Cao H, Zhang T, Shen H, Dong W, Wang L and Du J: The effect of diabetes mellitus on lung cancer prognosis: A PRISMA-compliant meta-analysis of cohort studies. Medicine (Baltimore). 95:e35282016. View Article : Google Scholar : PubMed/NCBI
27	Renehan AG, Frystyk J and Flyvbjerg A: Obesity and cancer risk: The role of the insulin-IGF axis. Trends Endocrinol Metab. 17:328–336. 2006. View Article : Google Scholar : PubMed/NCBI
28	Papa V, Pezzino V, Costantino A, Belfiore A, Giuffrida D, Frittitta L, Vannelli GB, Brand R, Goldfine ID and Vigneri R: Elevated insulin receptor content in human breast cancer. J Clin Invest. 86:1503–1510. 1990. View Article : Google Scholar : PubMed/NCBI
29	Pollak MN, Schernhammer ES and Hankinson SE: Insulin-like growth factors and neoplasia. Nat Rev Cancer. 4:505–518. 2004. View Article : Google Scholar : PubMed/NCBI
30	Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, Pollak M, Regensteiner JG and Yee D: Diabetes and cancer: A consensus report. Diabetes Care. 33:1674–1685. 2010. View Article : Google Scholar : PubMed/NCBI
31	Li F, Liu Y, Ren L, Sun Q and Luo YX: IGF-1 regulates Ang II and VEGF signaling pathways in retinal neovascularization. Eur Rev Med Pharmacol Sci. 22:6175–6180. 2018.PubMed/NCBI
32	Surgucheva IG, Sivak JM, Fini ME, Palazzo RE and Surguchov AP: Effect of gamma-synuclein overexpression on matrix metalloproteinases in retinoblastoma Y79 cells. Arch Biochem Biophys. 410:167–176. 2003. View Article : Google Scholar : PubMed/NCBI
33	Jiang Y, Liu YE, Goldberg ID and Shi YE: γ synuclein, a novel heat-shock protein-associated chaperone, stimulates ligand-dependent estrogen receptor α signaling and mammary tumorigenesis. Cancer Res. 64:4539–4546. 2004. View Article : Google Scholar : PubMed/NCBI
34	Shen P-H, Fan Q-X, Li Y-W, Zhang W, He XK, Wang Z and Zhang YH: SNCG shRNA suppressed breast cancer cell xenograft formation and growth in nude mice. Chin Med J (Engl). 124:1524–1528. 2011.PubMed/NCBI
35	Alexa A, Gógl G, Glatz G, Garai Á, Zeke A, Varga J, Dudás E, Jeszenői N, Bodor A, Hetényi C, et al: Structural assembly of the signaling competent ERK2-RSK1 heterodimeric protein kinase complex. Proc Natl Acad Sci USA. 112:2711–2716. 2015. View Article : Google Scholar : PubMed/NCBI
36	Liu K, Lu R, Zhao Q, Du J, Li Y, Zheng M and Zhang S: Association and clinicopathologic significance of p38MAPK-ERK-JNK-CDC25C with polyploid giant cancer cell formation. Med Oncol. 37:62019. View Article : Google Scholar : PubMed/NCBI
37	Yang T, Wang Y, Zhan S, Jia Q and Wang X: Effects of ERK gene overexpression on proliferation, migration and invasion of lung cancer A549 Cells. J Ningxia Med Univ. 42:332–338. 2020.
38	Eisinger-Mathason TSK, Andrade J and Lannigan DA: RSK in tumorigenesis: Connections to steroid signaling. Steroids. 75:191–202. 2010. View Article : Google Scholar : PubMed/NCBI
39	Jian W, Xue-zhong H, Jing L and Jing G: The molecular mechanism of miR23a promotes apoptosis of lung cancer cell line A549 Caspase-3 expression. Anat Res. 40:494–497. 2018.
40	Fan C, Liu J, Tian J, Zhang Y, Yan M and Zhu C: siRNA Targeting of the SNCG gene inhibits the growth of gastric carcinoma SGC7901 cells in vitro and in vivo by downregulating the phosphorylation of AKT/ERK. Cytogenet Genome Res. 154:209–216. 2018. View Article : Google Scholar : PubMed/NCBI
41	Man GCW, Wang J, Song Y, Wong JH, Zhao Y, Lau TS, Leung KT, Chan TH, Wang H, Kwong J, et al: Therapeutic potential of a novel prodrug of green tea extract in induction of apoptosis via ERK/JNK and Akt signaling pathway in human endometrial cancer. BMC Cancer. 20:9642020. View Article : Google Scholar : PubMed/NCBI