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Published in: Tumor Biology 11/2016

01-11-2016 | Original Article

Novel long non-coding RNA GACAT3 promotes gastric cancer cell proliferation through the IL-6/STAT3 signaling pathway

Authors: Wanjing Shen, Yanyan Yuan, Ming Zhao, Jiahui Li, Jin Xu, Guoying Lou, Jiachen Zheng, Shizhong Bu, Junming Guo, Yang Xi

Published in: Tumor Biology | Issue 11/2016

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Abstract

Long non-coding RNAs (lncRNAs) play an important role in cancer occurrence and development. We previously demonstrated that lncRNA gastric cancer-associated transcript 3 (GACAT3) was positively correlated with TNM stages, tumor size, and distant metastasis of patients with gastric cancer. However, the role of GACAT3 in gastric cancer remains unclear. In this study, to investigate its function, we synthesized small interference RNAs (siRNAs) against GACTA3 and developed a GACAT3 overexpression vector (pcDNA3-GACAT3), respectively. The siRNA-mediated knockdown of GACAT3 significantly decreased cell proliferation of the gastric cancer HGC-27 cells, in which GACAT3 is overexpressed. Furthermore, GACAT3 overexpression in gastric cancer SGC-7901 cells promoted cell growth. Moreover, GACAT3 expression in HGC-27 cells was greatly upregulated by IL-6 treatment in a concentration-dependent manner. In contrast, siRNA-mediated knockdown of STAT3 decreased GACAT3 expression even in the presence of IL-6. These results demonstrated that as a downstream target of the IL6/STAT3 signaling, lncRNA GACAT3 promotes gastric cancer cell growth suggesting that GACAT3 is an inflammatory response gene and may be served as a valuable potential target for the treatment of gastric cancer.
Literature
1.
go back to reference Ferro A, Peleteiro B, Malvezzi M, Bosetti C, Bertuccio P, Levi F, et al. Worldwide trends in gastric cancer mortality (1980–2011), with predictions to 2015, and incidence by subtype. Eur J Cancer. 2014;50:1330–44.CrossRefPubMed Ferro A, Peleteiro B, Malvezzi M, Bosetti C, Bertuccio P, Levi F, et al. Worldwide trends in gastric cancer mortality (1980–2011), with predictions to 2015, and incidence by subtype. Eur J Cancer. 2014;50:1330–44.CrossRefPubMed
2.
go back to reference Wang K, Liang Q, Li X, Tsoi H, Zhang J, Wang H, et al. MDGA2 is a novel tumour suppressor cooperating with dmap1 in gastric cancer and is associated with disease outcome. Gut. 2015. doi:10.1136/gutjnl-2015-309276. Wang K, Liang Q, Li X, Tsoi H, Zhang J, Wang H, et al. MDGA2 is a novel tumour suppressor cooperating with dmap1 in gastric cancer and is associated with disease outcome. Gut. 2015. doi:10.​1136/​gutjnl-2015-309276.
3.
go back to reference Correa P, Piazuelo MB, Camargo MC. The future of gastric cancer prevention. Gastric Cancer. 2004;7:9–16.CrossRefPubMed Correa P, Piazuelo MB, Camargo MC. The future of gastric cancer prevention. Gastric Cancer. 2004;7:9–16.CrossRefPubMed
4.
go back to reference Shah MA, Kelsen DP. Gastric cancer: a primer on the epidemiology and biology of the disease and an overview of the medical management of advanced disease. J Natl Compr Cancer Netw. 2010;8:437–47. Shah MA, Kelsen DP. Gastric cancer: a primer on the epidemiology and biology of the disease and an overview of the medical management of advanced disease. J Natl Compr Cancer Netw. 2010;8:437–47.
5.
go back to reference Stewart BW, Wild CP, editors. World cancer report 2014. Lyon: International Agency for Research on Cancer; 2014. p. 2014. Stewart BW, Wild CP, editors. World cancer report 2014. Lyon: International Agency for Research on Cancer; 2014. p. 2014.
6.
7.
go back to reference Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10:155–9.CrossRefPubMed Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10:155–9.CrossRefPubMed
8.
9.
go back to reference Xie SS, Jin J, Xu X, Zhuo W, Zhou TH. Emerging roles of non-coding rnas in gastric cancer: pathogenesis and clinical implications. World J Gastroenterol. 2016;22:1213–23.CrossRefPubMedPubMedCentral Xie SS, Jin J, Xu X, Zhuo W, Zhou TH. Emerging roles of non-coding rnas in gastric cancer: pathogenesis and clinical implications. World J Gastroenterol. 2016;22:1213–23.CrossRefPubMedPubMedCentral
11.
go back to reference Song H, Sun W, Ye G, Ding X, Liu Z, Zhang S, et al. Long non-coding rna expression profile in human gastric cancer and its clinical significances. J Transl Med. 2013;11:225.CrossRefPubMedPubMedCentral Song H, Sun W, Ye G, Ding X, Liu Z, Zhang S, et al. Long non-coding rna expression profile in human gastric cancer and its clinical significances. J Transl Med. 2013;11:225.CrossRefPubMedPubMedCentral
12.
go back to reference Xia T, Liao Q, Jiang X, Shao Y, Xiao B, Xi Y, et al. Long noncoding RNA associated-competing endogenous RNAs in gastric cancer. Sci Rep. 2014;4:6088.PubMedPubMedCentral Xia T, Liao Q, Jiang X, Shao Y, Xiao B, Xi Y, et al. Long noncoding RNA associated-competing endogenous RNAs in gastric cancer. Sci Rep. 2014;4:6088.PubMedPubMedCentral
13.
go back to reference Chen S, Li P, Xiao B, Guo J. Long noncoding RNA hmlincrna717 and ac130710 have been officially named as gastric cancer associated transcript 2 (gacat2) and gacat3, respectively. Tumor Biol. 2014;35:8351–2.CrossRef Chen S, Li P, Xiao B, Guo J. Long noncoding RNA hmlincrna717 and ac130710 have been officially named as gastric cancer associated transcript 2 (gacat2) and gacat3, respectively. Tumor Biol. 2014;35:8351–2.CrossRef
14.
go back to reference Xu C, Shao Y, Xia T, Yang Y, Dai J, Luo L, et al. Lncrna-ac130710 targeting by mir-129-5p is upregulated in gastric cancer and associates with poor prognosis. Tumor Biol. 2014;35:9701–6.CrossRef Xu C, Shao Y, Xia T, Yang Y, Dai J, Luo L, et al. Lncrna-ac130710 targeting by mir-129-5p is upregulated in gastric cancer and associates with poor prognosis. Tumor Biol. 2014;35:9701–6.CrossRef
15.
go back to reference Yu X, Song H, Xia T, Han S, Xiao B, Luo L, et al. Growth inhibitory effects of three mir-129 family members on gastric cancer. Gene. 2013;532:87–93.CrossRefPubMed Yu X, Song H, Xia T, Han S, Xiao B, Luo L, et al. Growth inhibitory effects of three mir-129 family members on gastric cancer. Gene. 2013;532:87–93.CrossRefPubMed
16.
go back to reference Madej-Michniewicz A, Budkowska M, Salata D, Dolegowska B, Starzynska T, Blogowski W. Evaluation of selected interleukins in patients with different gastric neoplasms: a preliminary report. Sci Rep. 2015;5:14382.CrossRefPubMedPubMedCentral Madej-Michniewicz A, Budkowska M, Salata D, Dolegowska B, Starzynska T, Blogowski W. Evaluation of selected interleukins in patients with different gastric neoplasms: a preliminary report. Sci Rep. 2015;5:14382.CrossRefPubMedPubMedCentral
18.
go back to reference Aggarwal BB, Kunnumakkara AB, Harikumar KB, Gupta SR, Tharakan ST, Koca C, et al. Signal transducer and activator of transcription-3, inflammation, and cancer: how intimate is the relationship? Ann N Y Acad Sci. 2009;1171:59–76.CrossRefPubMedPubMedCentral Aggarwal BB, Kunnumakkara AB, Harikumar KB, Gupta SR, Tharakan ST, Koca C, et al. Signal transducer and activator of transcription-3, inflammation, and cancer: how intimate is the relationship? Ann N Y Acad Sci. 2009;1171:59–76.CrossRefPubMedPubMedCentral
20.
go back to reference Frank DA. Stat signaling in cancer: insights into pathogenesis and treatment strategies. Cancer Treat Res. 2003;115:267–91.CrossRefPubMed Frank DA. Stat signaling in cancer: insights into pathogenesis and treatment strategies. Cancer Treat Res. 2003;115:267–91.CrossRefPubMed
21.
go back to reference Kanda N, Seno H, Konda Y, Marusawa H, Kanai M, Nakajima T, et al. Stat3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells. Oncogene. 2004;23:4921–9.CrossRefPubMed Kanda N, Seno H, Konda Y, Marusawa H, Kanai M, Nakajima T, et al. Stat3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells. Oncogene. 2004;23:4921–9.CrossRefPubMed
22.
go back to reference Hajimoradi M, Mohammad Hassan Z, Ebrahimi M, Soleimani M, Bakhshi M, Firouzi J, et al. STAT3 is overactivated in gastric cancer stem-like cells. Cell J. 2016;17:617–28.PubMedPubMedCentral Hajimoradi M, Mohammad Hassan Z, Ebrahimi M, Soleimani M, Bakhshi M, Firouzi J, et al. STAT3 is overactivated in gastric cancer stem-like cells. Cell J. 2016;17:617–28.PubMedPubMedCentral
23.
go back to reference Rokavec M, Oner MG, Li H, Jackstadt R, Jiang L, Lodygin D, et al. IL-6R/STAT3/miR-34a feedback loop promotes EMT-mediated colorectal cancer invasion and metastasis. J Clin Invest. 2015;125:1362.CrossRefPubMedPubMedCentral Rokavec M, Oner MG, Li H, Jackstadt R, Jiang L, Lodygin D, et al. IL-6R/STAT3/miR-34a feedback loop promotes EMT-mediated colorectal cancer invasion and metastasis. J Clin Invest. 2015;125:1362.CrossRefPubMedPubMedCentral
24.
go back to reference Chung SS, Giehl N, Wu Y, Vadgama JV. STAT3 activation in HER2-overexpressing breast cancer promotes epithelial-mesenchymal transition and cancer stem cell traits. Int J Oncol. 2014;44:403–11.PubMed Chung SS, Giehl N, Wu Y, Vadgama JV. STAT3 activation in HER2-overexpressing breast cancer promotes epithelial-mesenchymal transition and cancer stem cell traits. Int J Oncol. 2014;44:403–11.PubMed
25.
go back to reference Xi Y, Watanabe S, Hino Y, Sakamoto C, Nakatsu Y, Okada S, et al. Hmga1 is differentially expressed and mediates silencing of the CD4/CD8 loci in T cell lineages and leukemic cells. Cancer Sci. 2012;103:439–47.CrossRefPubMed Xi Y, Watanabe S, Hino Y, Sakamoto C, Nakatsu Y, Okada S, et al. Hmga1 is differentially expressed and mediates silencing of the CD4/CD8 loci in T cell lineages and leukemic cells. Cancer Sci. 2012;103:439–47.CrossRefPubMed
26.
go back to reference Shi X, Sun M, Liu H, Yao Y, Song Y. Long non-coding RNAs: a new frontier in the study of human diseases. Cancer Lett. 2013;339:159–66.CrossRefPubMed Shi X, Sun M, Liu H, Yao Y, Song Y. Long non-coding RNAs: a new frontier in the study of human diseases. Cancer Lett. 2013;339:159–66.CrossRefPubMed
27.
go back to reference Zhao J, Liu Y, Huang G, Cui P, Zhang W, Zhang Y. Long non-coding RNAs in gastric cancer: versatile mechanisms and potential for clinical translation. Am J Cancer Res. 2015;5:907–27.PubMedPubMedCentral Zhao J, Liu Y, Huang G, Cui P, Zhang W, Zhang Y. Long non-coding RNAs in gastric cancer: versatile mechanisms and potential for clinical translation. Am J Cancer Res. 2015;5:907–27.PubMedPubMedCentral
28.
go back to reference Lu MH, Tang B, Zeng S, Hu CJ, Xie R, Wu YY, et al. Long noncoding RNA BC032469, a novel competing endogenous RNA, upregulates hTERT expression by sponging miR-1207-5p and promotes proliferation in gastric cancer. Oncogene. 2015. doi:10.1038/onc.2015.413. Lu MH, Tang B, Zeng S, Hu CJ, Xie R, Wu YY, et al. Long noncoding RNA BC032469, a novel competing endogenous RNA, upregulates hTERT expression by sponging miR-1207-5p and promotes proliferation in gastric cancer. Oncogene. 2015. doi:10.​1038/​onc.​2015.​413.
29.
go back to reference Yang F, Xue X, Zheng L, Bi J, Zhou Y, Zhi K, et al. Long non-coding RNA GHET1 promotes gastric carcinoma cell proliferation by increasing c-Myc mRNA stability. FEBS J. 2014;281:802–13.CrossRefPubMed Yang F, Xue X, Zheng L, Bi J, Zhou Y, Zhi K, et al. Long non-coding RNA GHET1 promotes gastric carcinoma cell proliferation by increasing c-Myc mRNA stability. FEBS J. 2014;281:802–13.CrossRefPubMed
30.
go back to reference Wang Z, Si X, Xu A, Meng X, Gao S, Qi Y, et al. Activation of STAT3 in human gastric cancer cells via interleukin (IL)-6-type cytokine signaling correlates with clinical implications. PLoS One. 2013;8:e75788.CrossRefPubMedPubMedCentral Wang Z, Si X, Xu A, Meng X, Gao S, Qi Y, et al. Activation of STAT3 in human gastric cancer cells via interleukin (IL)-6-type cytokine signaling correlates with clinical implications. PLoS One. 2013;8:e75788.CrossRefPubMedPubMedCentral
31.
go back to reference Judd LM, Menheniott TR, Ling H, Jackson CB, Howlett M, Kalantzis A, et al. Inhibition of the JAK2/STAT3 pathway reduces gastric cancer growth in vitro and in vivo. PLoS One. 2014;9:e95993.CrossRefPubMedPubMedCentral Judd LM, Menheniott TR, Ling H, Jackson CB, Howlett M, Kalantzis A, et al. Inhibition of the JAK2/STAT3 pathway reduces gastric cancer growth in vitro and in vivo. PLoS One. 2014;9:e95993.CrossRefPubMedPubMedCentral
32.
go back to reference Zhong Z, Wen Z, Darnell Jr JE. Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science. 1994;264:95–8.CrossRefPubMed Zhong Z, Wen Z, Darnell Jr JE. Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science. 1994;264:95–8.CrossRefPubMed
33.
go back to reference Masuda M, Suzui M, Yasumatu R, Nakashima T, Kuratomi Y, Azuma K, et al. Constitutive activation of signal transducers and activators of transcription 3 correlates with cyclin D1 overexpression and may provide a novel prognostic marker in head and neck squamous cell carcinoma. Cancer Res. 2002;62:3351–5.PubMed Masuda M, Suzui M, Yasumatu R, Nakashima T, Kuratomi Y, Azuma K, et al. Constitutive activation of signal transducers and activators of transcription 3 correlates with cyclin D1 overexpression and may provide a novel prognostic marker in head and neck squamous cell carcinoma. Cancer Res. 2002;62:3351–5.PubMed
34.
go back to reference Gortz D, Braun GS, Maruta Y, Djudjaj S, van Roeyen CR, Martin IV, et al. Anti-interleukin-6 therapy through application of a monogenic protein inhibitor via gene delivery. Sci Rep. 2015;5:14685.CrossRefPubMedPubMedCentral Gortz D, Braun GS, Maruta Y, Djudjaj S, van Roeyen CR, Martin IV, et al. Anti-interleukin-6 therapy through application of a monogenic protein inhibitor via gene delivery. Sci Rep. 2015;5:14685.CrossRefPubMedPubMedCentral
Metadata
Title
Novel long non-coding RNA GACAT3 promotes gastric cancer cell proliferation through the IL-6/STAT3 signaling pathway
Authors
Wanjing Shen
Yanyan Yuan
Ming Zhao
Jiahui Li
Jin Xu
Guoying Lou
Jiachen Zheng
Shizhong Bu
Junming Guo
Yang Xi
Publication date
01-11-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 11/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5372-8

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