Specificity protein 1‑activated bone marrow stromal cell antigen 2 accelerates pancreatic cancer cell proliferation and migration

Lei,Chun; Hou,Yafeng; Chen,Jiong

doi:10.3892/etm.2021.10894

Specificity protein 1‑activated bone marrow stromal cell antigen 2 accelerates pancreatic cancer cell proliferation and migration

Authors:
- Chun Lei
- Yafeng Hou
- Jiong Chen
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Affiliations: Department of General Surgery, Tongling People's Hospital, Tongling, Anhui 244009, P.R. China, Department of General Surgery, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, Anhui 230001, P.R. China
Published online on: October 20, 2021 https://doi.org/10.3892/etm.2021.10894
Article Number: 1459
Copyright: © Lei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bone marrow stromal cell antigen 2 (BST2) has been reported to act as an oncogene in the tumorigenesis of numerous types of cancer. Bioinformatics analysis has predicted the binding interaction between BST2 and specificity protein 1 (SP1) and the involvement of SP1 in pancreatic cancer. Therefore, the present study set out to verify this interaction and determine how it may affect pancreatic cancer progression. Normal human pancreatic duct epithelial cells (HPDE6‑C7) and pancreatic cancer cell lines (SW1990, BxPC3, PANC1 and PSN‑1) were selected for western blotting and reverse transcription‑quantitative PCR detection of BST2 expression. Colony formation, Cell Counting Kit‑8 and wound healing assays were performed to detect the proliferative and migratory abilities of PANC1 cells following transfection with small interfering RNA against BST2. The expression of proliferation and migration markers were assayed using western blotting. Chromatin immunoprecipitation and luciferase reporter assays were employed to verify the bioinformatics prediction of BST2‑SP1 binding. PANC1 cell proliferation and migration were analyzed following BST2 knockdown and SP1 overexpression. In comparison with HPDE6‑C7 cells, all four pancreatic cancer cell lines were found to exhibit increased BST2 expression levels to varying degrees, with the highest levels observed in PANC1 cells. BST2 knockdown inhibited PANC1 cell colony formation, proliferation and migration. Additionally, SP1 was shown to bind to the BST2 promoter and could promote PANC1 cell proliferation and migration when overexpressed. However, BST2 knockdown rescued SP1 overexpression‑induced PANC1 cell colony formation, proliferation and migration. In conclusion, activation of BST2 by the transcription factor SP1 was shown to accelerate pancreatic cancer cell proliferation and migration, suggesting that BST2 and SP1 may be plausible therapeutic targets in targeted therapy for pancreatic cancer.

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1	Vincent A, Herman J, Schulick R, Hruban RH and Goggins M: Pancreatic cancer. Lancet. 378:607–620. 2011.PubMed/NCBI View Article : Google Scholar
2	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018.PubMed/NCBI View Article : Google Scholar
3	Ilic M and Ilic I: Epidemiology of pancreatic cancer. World J Gastroenterol. 22:9694–9705. 2016.PubMed/NCBI View Article : Google Scholar
4	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2019. CA Cancer J Clin. 69:7–34. 2019.PubMed/NCBI View Article : Google Scholar
5	Mizrahi JD, Surana R, Valle JW and Shroff RT: Pancreatic cancer. Lancet. 395:2008–2020. 2020.PubMed/NCBI View Article : Google Scholar
6	Qian L, Yu S, Chen Z, Meng Z, Huang S and Wang P: Functions and clinical implications of exosomes in pancreatic cancer. Biochim Biophys Acta Rev Cancer. 1871:75–84. 2019.PubMed/NCBI View Article : Google Scholar
7	Zhang L, Sanagapalli S and Stoita A: Challenges in diagnosis of pancreatic cancer. World J Gastroenterol. 24:2047–2060. 2018.PubMed/NCBI View Article : Google Scholar
8	Yang J, Ren B, Yang G, Wang H, Chen G, You L, Zhang T and Zhao Y: The enhancement of glycolysis regulates pancreatic cancer metastasis. Cell Mol Life Sci. 77:305–321. 2020.PubMed/NCBI View Article : Google Scholar
9	Rouanet M, Lebrin M, Gross F, Bournet B, Cordelier P and Buscail L: Gene Therapy for Pancreatic Cancer: Specificity, Issues and Hopes. Int J Mol Sci. 18(1231)2017.PubMed/NCBI View Article : Google Scholar
10	Kurtanich T, Roos N, Wang G, Yang J, Wang A and Chung EJ: Pancreatic Cancer Gene Therapy Delivered by Nanoparticles. SLAS Technol. 24:151–160. 2019.PubMed/NCBI View Article : Google Scholar
11	Wu J, Li Z, Zeng K, Wu K, Xu D, Zhou J and Xu L: Key genes associated with pancreatic cancer and their association with outcomes: A bioinformatics analysis. Mol Med Rep. 20:1343–1352. 2019.PubMed/NCBI View Article : Google Scholar
12	Arnaud F, Black SG, Murphy L, Griffiths DJ, Neil SJ, Spencer TE and Palmarini M: Interplay between ovine bone marrow stromal cell antigen 2/tetherin and endogenous retroviruses. J Virol. 84:4415–4425. 2010.PubMed/NCBI View Article : Google Scholar
13	Gong S, Osei ES, Kaplan D, Chen YH and Meyerson H: CD317 is over-expressed in B-cell chronic lymphocytic leukemia, but not B-cell acute lymphoblastic leukemia. Int J Clin Exp Pathol. 8:1613–1621. 2015.PubMed/NCBI
14	Wang W, Nishioka Y, Ozaki S, Jalili A, Abe S, Kakiuchi S, Kishuku M, Minakuchi K, Matsumoto T and Sone S: HM1.24 (CD317) is a novel target against lung cancer for immunotherapy using anti-HM1.24 antibody. Cancer Immunol Immunother. 58:967–976. 2009.PubMed/NCBI View Article : Google Scholar
15	Malsy M, Graf B and Almstedt K: The active role of the transcription factor Sp1 in NFATc2-mediated gene regulation in pancreatic cancer. BMC Biochem. 20(2)2019.PubMed/NCBI View Article : Google Scholar
16	Safe S, Nair V and Karki K: Metformin-induced anticancer activities: Recent insights. Biol Chem. 399:321–335. 2018.PubMed/NCBI View Article : Google Scholar
17	Nair V, Pathi S, Jutooru I, Sreevalsan S, Basha R, Abdelrahim M, Samudio I and Safe S: Metformin inhibits pancreatic cancer cell and tumor growth and downregulates Sp transcription factors. Carcinogenesis. 34:2870–2879. 2013.PubMed/NCBI View Article : Google Scholar
18	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.PubMed/NCBI View Article : Google Scholar
19	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016.PubMed/NCBI View Article : Google Scholar
20	Hogendorf P, Durczyński A and Strzelczyk J: Metastatic Pancreatic Cancer. J Invest Surg. 31:151–152. 2018.PubMed/NCBI View Article : Google Scholar
21	Ferrone CR, Brennan MF, Gonen M, Coit DG, Fong Y, Chung S, Tang L, Klimstra D and Allen PJ: Pancreatic adenocarcinoma: The actual 5-year survivors. J Gastrointest Surg. 12:701–706. 2008.PubMed/NCBI View Article : Google Scholar
22	Hackert T, Klaiber U, Pausch T, Mihaljevic AL and Büchler MW: Fifty Years of Surgery for Pancreatic Cancer. Pancreas. 49:1005–1013. 2020.PubMed/NCBI View Article : Google Scholar
23	Das S and Batra SK: Pancreatic cancer metastasis: Are we being pre-EMTed? Curr Pharm Des. 21:1249–1255. 2015.PubMed/NCBI View Article : Google Scholar
24	Ishikawa J, Kaisho T, Tomizawa H, Lee BO, Kobune Y, Inazawa J, Oritani K, Itoh M, Ochi T, Ishihara K, et al: Molecular cloning and chromosomal mapping of a bone marrow stromal cell surface gene, BST2, that may be involved in pre-B-cell growth. Genomics. 26:527–534. 1995.PubMed/NCBI View Article : Google Scholar
25	Fujiwara K, Ohuchida K, Sada M, Horioka K, Ulrich CD III, Shindo K, Ohtsuka T, Takahata S, Mizumoto K, Oda Y, et al: CD166/ALCAM expression is characteristic of tumorigenicity and invasive and migratory activities of pancreatic cancer cells. PLoS One. 9(e107247)2014.PubMed/NCBI View Article : Google Scholar
26	Xu X, Wang Y, Xue F, Guan E, Tian F, Xu J and Zhang H: BST2 Promotes Tumor Growth via Multiple Pathways in Hepatocellular Carcinoma. Cancer Invest. 38:329–337. 2020.PubMed/NCBI View Article : Google Scholar
27	Liu W, Li Y, Feng S, Guan Y and Cao Y: MicroRNA-760 inhibits cell viability and migration through down-regulating BST2 in gastric cancer. J Biochem. 168:159–170. 2020.PubMed/NCBI View Article : Google Scholar
28	Liu W, Cao Y, Guan Y and Zheng C: BST2 promotes cell proliferation, migration and induces NF-κB activation in gastric cancer. Biotechnol Lett. 40:1015–1027. 2018.PubMed/NCBI View Article : Google Scholar
29	Zhang X, Zhuang H, Han F, Shao X, Liu Y, Ma X, Wang Z, Qiang Z and Li Y: Sp1-regulated transcription of RasGRP1 promotes hepatocellular carcinoma (HCC) proliferation. Liver Int. 38:2006–2017. 2018.PubMed/NCBI View Article : Google Scholar
30	Peng X, Wu M, Liu W, Guo C, Zhan L and Zhan X: miR-502-5p inhibits the proliferation, migration and invasion of gastric cancer cells by targeting SP1. Oncol Lett. 20:2757–2762. 2020.PubMed/NCBI View Article : Google Scholar
31	Xue L, Shen Y, Zhai Z and Zheng S: miR 539 suppresses the proliferation, migration, invasion and epithelial mesenchymal transition of pancreatic cancer cells through targeting SP1. Int J Mol Med. 45:1771–1782. 2020.PubMed/NCBI View Article : Google Scholar
32	Mi LD, Sun CX, He SW and Du GY: SP1-Induced Upregulation of lncRNA LINC00514 Promotes Tumor Proliferation and Metastasis in Osteosarcoma by Regulating miR-708. Cancer Manag Res. 12:3311–3322. 2020.PubMed/NCBI View Article : Google Scholar
33	Bai Z, Wu Y, Bai S, Yan Y, Kang H, Ma W, Zhang J, Gao Y, Hui B, Ma H, et al: Long non-coding RNA SNGH7 Is activated by SP1 and exerts oncogenic properties by interacting with EZH2 in ovarian cancer. J Cell Mol Med. 24:7479–7489. 2020.PubMed/NCBI View Article : Google Scholar