Knockdown of CREB1 inhibits tumor growth of human gastric cancer in vitro and in vivo Retraction in /10.3892/or.2021.8202

Rao,Min; Zhu,Yonggang; Cong,Xiaoxia; Li,Qianxun

doi:10.3892/or.2017.5636

Knockdown of CREB1 inhibits tumor growth of human gastric cancer in vitro and in vivo

Retraction in: /10.3892/or.2021.8202

Authors:
- Min Rao
- Yonggang Zhu
- Xiaoxia Cong
- Qianxun Li
View Affiliations

Affiliations: Department of Gastroenterology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Radiotherapy, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, Department of Gastroenterology, The People's Hospital of Jilin Province, Changchun, Jilin 130021, P.R. China
Published online on: May 11, 2017 https://doi.org/10.3892/or.2017.5636
Pages: 3361-3368

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

cAMP responsive element binding protein 1 (CREB1) gene, has been reported to play crucial roles in tumor progression and development in various types of cancer. Little is known, however, about its role and underlying mechanism in gastric cancer (GC). Herein, we investigated the biological roles and molecular mechanism of CREB1 in GC. The expression level was determined in four GC cell lines by quantitative RT-PCR and western blotting. Recombinant expression vector carrying small interfering RNA (siRNA) targeting CREB1 was constructed and then transfected into human GC cell line (SGC-7901). Cell proliferation, colony formation, cycle distribution, migration and invasion in vitro were determined by MTT, colony forming, flow cytometry, would healing and Transwell invasion assays after CREB1 knockdown. Tumor growth in vivo was assessed by measurement of tumor volume and weight in a nude mouse model. We found that CREB1 was highly expressed in the human GC cell lines. We also showed that knockdown of CREB1 in SGC-7901 cells significantly inhibited cell proliferation, colony formation, migration and invasion and induced cell arrest at G1/G0 phase in vitro, as well as suppressed tumor growth in vivo. In addition, CREB1 knockdown was able to significantly reduce expression of its downstream target genes cyclin D1, Bcl-2 and MMP-9 in vitro and in vivo. These findings suggest that CREB1 may be a potential therapeutic target for the treatment of gastric cancer.

View Figures

View References

1	Kamangar F, Dores GM and Anderson WF: Patterns of cancer incidence, mortality, and prevalence across five continents: Defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 24:2137–2150. 2006. View Article : Google Scholar : PubMed/NCBI
2	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
3	Orditura M, Galizia G, Sforza V, Gambardella V, Fabozzi A, Laterza MM, Andreozzi F, Ventriglia J, Savastano B, Mabilia A, et al: Treatment of gastric cancer. World J Gastroenterol. 20:1635–1649. 2014. View Article : Google Scholar : PubMed/NCBI
4	Shaywitz AJ and Greenberg ME: CREB: A stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu Rev Biochem. 68:821–861. 1999. View Article : Google Scholar : PubMed/NCBI
5	Rudolph D, Tafuri A, Gass P, Hämmerling GJ, Arnold B and Schütz G: Impaired fetal T cell development and perinatal lethality in mice lacking the cAMP response element binding protein. Proc Natl Acad Sci USA. 95:pp. 4481–4486. 1998; View Article : Google Scholar : PubMed/NCBI
6	Mayr B and Montminy M: Transcriptional regulation by the phosphorylation-dependent factor CREB. Nat Rev Mol Cell Biol. 2:599–609. 2001. View Article : Google Scholar : PubMed/NCBI
7	Sakamoto KM and Frank DA: CREB in the pathophysiology of cancer: implications for targeting transcription factors for cancer therapy. Clin Cancer Res. 15:2583–2587. 2009. View Article : Google Scholar : PubMed/NCBI
8	Park JK, Park SH, So K, Bae IH, Yoo YD and Um HD: ICAM-3 enhances the migratory and invasive potential of human non-small cell lung cancer cells by inducing MMP-2 and MMP-9 via Akt and CREB. Int J Oncol. 36:181–192. 2010.PubMed/NCBI
9	Zhang M, Xu JJ, Zhou RL and Zhang QY: cAMP responsive element binding protein-1 is a transcription factor of lysosomal-associated protein transmembrane-4 beta in human breast cancer cells. PLoS One. 8:e575202013. View Article : Google Scholar : PubMed/NCBI
10	Cheng JC, Esparza S, Sandoval S, Shankar D, Fu C and Sakamoto KM: Potential role of CREB as a prognostic marker in acute myeloid leukemia. Future Oncol. 3:475–480. 2007. View Article : Google Scholar : PubMed/NCBI
11	Guo YH, Wang LQ, Li B, Xu H, Yang JH, Zheng LS, Yu P, Zhou AD, Zhang Y, Xie SJ, et al: Wnt/β-catenin pathway transactivates microRNA-150 that promotes EMT of colorectal cancer cells by suppressing CREB signaling. Oncotarget. 7:42513–42526. 2016.PubMed/NCBI
12	Tan X, Wang S, Zhu L, Wu C, Yin B, Zhao J, Yuan J, Qiang B and Peng X: cAMP response element-binding protein promotes gliomagenesis by modulating the expression of oncogenic microRNA-23a. Proc Natl Acad Sci USA. 109:pp. 15805–15810. 2012; View Article : Google Scholar : PubMed/NCBI
13	Singh R, Shankar BS and Sainis KB: TGF-β1-ROS-ATM-CREB signaling axis in macrophage mediated migration of human breast cancer MCF7 cells. Cell Signal. 26:1604–1615. 2014. View Article : Google Scholar : PubMed/NCBI
14	Kinjo K, Sandoval S, Sakamoto KM and Shankar DB: The role of CREB as a proto-oncogene in hematopoiesis. Cell Cycle. 4:1134–1135. 2005. View Article : Google Scholar : PubMed/NCBI
15	Wang YW, Chen X, Ma R and Gao P: Understanding the CREB1-miRNA feedback loop in human malignancies. Tumour Biol. 37:8487–8502. 2016. View Article : Google Scholar : PubMed/NCBI
16	Wang YW, Chen X, Gao JW, Zhang H, Ma RR, Gao ZH and Gao P: High expression of cAMP-responsive element-binding protein 1 (CREB1) is associated with metastasis, tumor stage and poor outcome in gastric cancer. Oncotarget. 6:10646–10657. 2015. View Article : Google Scholar : PubMed/NCBI
17	Oerlecke I, Bauer E, Dittmer A, Leyh B and Dittmer J: Cyclic AMP enhances TGFβ responses of breast cancer cells by upregulating TGFβ receptor I expression. PLoS One. 8:e542612013. View Article : Google Scholar : PubMed/NCBI
18	Mihmanli M, Ilhan E, Idiz UO, Alemdar A and Demir U: Recent developments and innovations in gastric cancer. World J Gastroenterol. 22:4307–4320. 2016. View Article : Google Scholar : PubMed/NCBI
19	Digklia A and Wagner AD: Advanced gastric cancer: Current treatment landscape and future perspectives. World J Gastroenterol. 22:2403–2414. 2016. View Article : Google Scholar : PubMed/NCBI
20	Cetin B, Gumusay O, Cengiz M and Ozet A: Advances of molecular targeted therapy in gastric cancer. J Gastrointest Cancer. 47:125–134. 2016. View Article : Google Scholar : PubMed/NCBI
21	Morishita A, Gong J and Masaki T: Targeting receptor tyrosine kinases in gastric cancer. World J Gastroenterol. 20:4536–4545. 2014. View Article : Google Scholar : PubMed/NCBI
22	Giraud AS, Menheniott TR and Judd LM: Targeting STAT3 in gastric cancer. Expert Opin Ther Targets. 16:889–901. 2012. View Article : Google Scholar : PubMed/NCBI
23	Peng B, Hu S, Jun Q, Luo D, Zhang X, Zhao H and Li D: MicroRNA-200b targets CREB1 and suppresses cell growth in human malignant glioma. Mol Cell Biochem. 379:51–58. 2013. View Article : Google Scholar : PubMed/NCBI
24	Li P, Xue WJ, Feng Y and Mao QS: MicroRNA-205 functions as a tumor suppressor in colorectal cancer by targeting cAMP responsive element binding protein 1 (CREB1). Am J Transl Res. 7:2053–2059. 2015.PubMed/NCBI
25	Shukla A, Bosenberg MW, MacPherson MB, Butnor KJ, Heintz NH, Pass HI, Carbone M, Testa JR and Mossman BT: Activated cAMP response element binding protein is overexpressed in human mesotheliomas and inhibits apoptosis. Am J Pathol. 175:2197–2206. 2009. View Article : Google Scholar : PubMed/NCBI
26	Kong WQ, Bai R, Liu T, Cai CL, Liu M, Li X and Tang H: MicroRNA-182 targets cAMP-responsive element-binding protein 1 and suppresses cell growth in human gastric adenocarcinoma. FEBS J. 279:1252–1260. 2012. View Article : Google Scholar : PubMed/NCBI
27	Zhang X, Odom DT, Koo SH, Conkright MD, Canettieri G, Best J, Chen H, Jenner R, Herbolsheimer E, Jacobsen E, et al: Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues. Proc Natl Acad Sci USA. 102:pp. 4459–4464. 2005; View Article : Google Scholar : PubMed/NCBI