Effects of stromal interacting molecule 1 gene silencing by short hairpin RNA on the biological behavior of human gastric cancer cells

Liu,Bin; Yu,Hai‑Hong; Ye,Hong‑Li; Luo,Zhi‑Ying; Xiao,Feng

doi:10.3892/mmr.2015.3778

Effects of stromal interacting molecule 1 gene silencing by short hairpin RNA on the biological behavior of human gastric cancer cells

Authors:
- Bin Liu
- Hai‑Hong Yu
- Hong‑Li Ye
- Zhi‑Ying Luo
- Feng Xiao
View Affiliations

Affiliations: Department of Pathology, Affiliated Hospital of Jinggangshan University, Ji'an, Jiangxi 343000, P.R. China, Ji'an Key Laboratory of Pharmaceutical Biotechnology, School of Medicine, Jinggangshan University, Ji'an, Jiangxi 343000, P.R. China, Department of Pathology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Pathology, School of Medicine, Jinggangshan University, Ji'an, Jiangxi 343000, P.R. China
Published online on: May 13, 2015 https://doi.org/10.3892/mmr.2015.3778
Pages: 3047-3054

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

Gastric cancer is one of the most common types of cancer worldwide. It has been reported that stromal interacting molecule 1 (STIM1) is associated with tumor progression and metastatic spread, including in cervical cancer, breast carcinoma and prostatic cancer. The present study investigated whether STIM1, an endoplasmic reticulum Ca2+ sensor and activator of store‑operated channel entry, contributed to SGC7901 cell progression. The pGPU6‑shSTIM1 recombinant plasmid was constructed, and the effects of downregulation of STIM1 on the proliferation, apoptosis, migration and invasion of SGC7901 cells were examined. Western blot analysis revealed that transfection with the pGPU6‑shSTIM1 plasmid successfully inhibited the expression of STIM1. STIM1 silencing in the gastric cancer cells significantly inhibited cell proliferation by arresting the cell cycle at the G0/G1 phase, and increasing the apoptotic rate following treatment of the SGC7901 cells with pGPU6‑shSTIM1, indicated using an MTT cell viability assay and flow cytometery, respectively. As expected, STIM1 knock down also reduced the migration and invasion of the SGC7901 cells, demonstrated using a Transwell assay. The possible molecular mechanism involved the regulation of several signaling pathways involved in the biological behavior of cell survival, apoptosis, migration and metastasis. Together, these finding suggested that the expression of STIM1 is crucial for the proliferation and invasion of SGC7901 cells, providing a foundation for the development of novel type‑specific diagnostic strategies and treatments for gastric cancer.

View Figures

View References

1	Ferlay J, Shin HR, Bray F, et al: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar
2	Jemal A, Bray F, Center MM, et al: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
3	Berridge MJ, Bootman MD and Roderick HL: Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol. 4:517–529. 2003. View Article : Google Scholar : PubMed/NCBI
4	Berridge MJ, Lipp P and Bootman MD: The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol. 1:11–21. 2000. View Article : Google Scholar
5	Putney JW Jr: A model for receptor-regulated calcium entry. Cell Calcium. 7:1–12. 1986. View Article : Google Scholar : PubMed/NCBI
6	Liou J, Kim ML, Heo WD, et al: STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. Curr Biol. 15:1235–1241. 2005. View Article : Google Scholar : PubMed/NCBI
7	Roos J, DiGregorio PJ, Yeromin AV, et al: STIM1, an essential and conserved component of store-operated Ca2+ channel function. J Cell Biol. 169:435–445. 2005. View Article : Google Scholar : PubMed/NCBI
8	Spassova MA, Soboloff J, He LP, et al: STIM1 has a plasma membrane role in the activation of store-operated Ca2+ channels. Proc Natl Acad Sci U S A. 103:4040–4045. 2006. View Article : Google Scholar : PubMed/NCBI
9	Sabbioni S, Barbanti-Brodano G, Croce CM and Negrini M: GOK: a gene at 11p15 involved in rhabdomyosarcoma and rhabdoid tumor development. Cancer Res. 57:4493–4497. 1997.PubMed/NCBI
10	Sabbioni S, Veronese A, Trubia M, et al: Exon structure and promoter identification of STIM1 (alias GOK), a human gene causing growth arrest of the human tumor cell lines G401 and RD. Cytogenet Cell Genet. 86:214–218. 1999. View Article : Google Scholar : PubMed/NCBI
11	Yang S, Zhang JJ and Huang XY: Orai1 and STIM1 are critical for breast tumor cell migration and metastasis. Cancer Cell. 15:124–134. 2009. View Article : Google Scholar : PubMed/NCBI
12	Liu H, Hughes JD, Rollins S, et al: Calcium entry via ORAI1 regulates glioblastoma cell proliferation and apoptosis. Exp Mol Pathol. 91:753–760. 2011. View Article : Google Scholar : PubMed/NCBI
13	Scrideli CA, Carlotti CG Jr, Okamoto OK, et al: Gene expression profile analysis of primary glioblastomas and non-neoplastic brain tissue: identification of potential target genes by oligonucleotide microarray and real-time quantitative PCR. J Neurooncol. 88:281–291. 2008. View Article : Google Scholar : PubMed/NCBI
14	Chen YF, Chiu WT, Chen YT, et al: Calcium store sensor stromal-interaction molecule 1-dependent signaling plays an important role in cervical cancer growth, migration and angiogenesis. Proc Natl Acad Sci USA. 108:15225–15230. 2011. View Article : Google Scholar
15	Timmons JA, Rao JN, Turner DJ, et al: Induced expression of STIM1 sensitizes intestinal epithelial cells to apoptosis by modulating store-operated Ca2+ influx. J Gastrointest Surg. 16:1397–1405. 2012. View Article : Google Scholar : PubMed/NCBI
16	Gerlier D and Thomasset N: Use of MTT colorimetric assay to measure cell activation. J Immunol Methods. 94:57–63. 1986. View Article : Google Scholar : PubMed/NCBI
17	Nunez R: DNA measurement and cell cycle analysis by flow cytometry. Curr Issues Mol Biol. 3:67–70. 2001.PubMed/NCBI
18	Albini A and Benelli R: The chemoinvasion assay: a method to assess tumor and endothelial cell invasion and its modulation. Nat Protoc. 2:504–511. 2007. View Article : Google Scholar : PubMed/NCBI
19	Xie Y, Wolff DW, Wei T, et al: Breast cancer migration and invasion depend on proteasome degradation of regulator of G-protein signaling 4. Cancer Res. 69:5743–5751. 2009. View Article : Google Scholar : PubMed/NCBI
20	Jemal A, Siegel R, Ward E, et al: Cancer statistics, 2007. CA Cancer J Clin. 57:43–66. 2007. View Article : Google Scholar : PubMed/NCBI
21	An JY, Cheong JH, Hyung WJ and Noh SH: Recent evolution of surgical treatment for gastric cancer in Korea. J Gastric Cancer. 11:1–6. 2011. View Article : Google Scholar : PubMed/NCBI
22	Higuchi K, Phan A and Ajani JA: Gastric cancer: advances in adjuvant and adjunct therapy. Curr Treat Options Oncol. 4:413–419. 2003. View Article : Google Scholar : PubMed/NCBI
23	Lin Y, Ueda J, Kikuchi S, Totsuka Y, Wei WQ, Qiao YL and Inoue M: Comparative epidemiology of gastric cancer between Japan and China. World J Gastroenterol. 17:4421–4428. 2011. View Article : Google Scholar : PubMed/NCBI
24	Catalano V, Labianca R, Beretta GD, Gatta G, de Braud F and Van Cutsem E: Gastric cancer. Crit Rev Oncol Hematol. 54:209–241. 2005. View Article : Google Scholar : PubMed/NCBI
25	Clark AJ, Diamond M, Elfline M and Petty HR: Calicum micro-domains form within neutrophils at the neutrophil-tumor cell synapse: role in antibody-dependent target cell apoptosis. Cancer Immunol Immunother. 59:149–159. 2010. View Article : Google Scholar
26	Schuhmann MK, Stegner D, Berna-Erro A, et al: Stromal interaction molecules 1 and 2 are key regulators of autoreactive T cell activation in murine autoimmune central nervous system inflammation. J Immunol. 184:1536–1542. 2010. View Article : Google Scholar
27	Bisaillon JM, Motiani RK, Gonzalez-Cobos JC, et al: Essential role for STIM1/Orai1-mediated calcium influx in PDGF-induced smooth muscle migration. Am J Physiol Cell Physiol. 298:C993–1005. 2010. View Article : Google Scholar : PubMed/NCBI
28	Hayashi C, Rittling S, Hayata T, et al: Serum osteopontin, an enhancer of tumor metastasis to bone, promotes B16 melanoma cell migration. J Cell Biochem. 101:979–986. 2007. View Article : Google Scholar : PubMed/NCBI
29	Motiani RK, Hyzinski-García MC, Zhang X, et al: STIM1 and Orai1 mediate CRAC channel activity and are essential for human glioblastoma invasion. Pflugers Arch. 465:1249–1260. 2013. View Article : Google Scholar : PubMed/NCBI
30	Abdullaev IF, Bisaillon JM, Potier M, et al: Stim1 and Orai1 mediate CRAC currents and store-operated calcium entry important for endothelial cell proliferation. Circ Res. 103:1289–1299. 2008. View Article : Google Scholar : PubMed/NCBI
31	Suyama E, Wadhwa R, Kaur K, et al: Identification of metastasis-related genes in a mouse model using a library of randomized ribozymes. J Biol Chem. 279:38083–38086. 2004. View Article : Google Scholar : PubMed/NCBI
32	Takahashi Y, Watanabe H, Murakami M, et al: Upregulation of TRPC1 is involved in Angiotensin II-induced vascular smooth muscle cell hypertrophy. J Mol Cell Cardiol. 41:10572006. View Article : Google Scholar
33	Xiao F, Liu B and Zhu QX: c-Jun N-terminal kinase is required for thermotherapy-induced apoptosis in human gastric cancer cells. World J Gastroenterol. 18:7348–7356. 2012 December 28; View Article : Google Scholar
34	Sun S, Li W, Zhang H, et al: Requirement for store-operated calcium entry in sodium butyrate-induced apoptosis in human colon cancer cells. Biosci Rep. 32:83–90. 2012. View Article : Google Scholar
35	Klein CA: Cancer. The metastasis cascade. Science. 321:1785–1787. 2008. View Article : Google Scholar : PubMed/NCBI