CREBRF promotes the proliferation of human gastric cancer cells via the AKT signaling pathway

Jiming Han; Lu Zhang; Jing Zhang; Qiuyu Jiang; Dongdong Tong; Xiaofei Wang; Xing Gao; Lingyu Zhao; Chen Huang

doi:10.14715/cmb/2018.64.5.6

Issue

Vol. 64 No. 5: Issue 5

Issue Published : May 1, 2018

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CREBRF promotes the proliferation of human gastric cancer cells via the AKT signaling pathway

https://doi.org/10.14715/cmb/2018.64.5.6

Jiming Han

Department of Cell Biology and Genetics/Key Laboratory of Environment and Genes Related to Diseases, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710049, Shaanxi Province, P.R. China

Lu Zhang

Department of Foreign Languages, Ming De College of Northwestern Polytechnical University, Xi'an 710124, Shaanxi Province, P.R. China

Jing Zhang

Qiuyu Jiang

Dongdong Tong

Xiaofei Wang

Xing Gao

Lingyu Zhao

Chen Huang

Corresponding Author(s) : Jiming Han

hchen@xjtu.edu.cn

Cellular and Molecular Biology, Vol. 64 No. 5: Issue 5
Article Published : April 30, 2018

Abstract

Gastric cancer (GC) is one of the most common malignant cancer around the world, however the mechanisms is still unclear. In the present study, we investigated the function of CREB3 regulatory factor (CREBRF) in human GC and explored its relevant molecular mechanism. We found that CREBRF was highly expressed in primary GC tissues and the expression level was associated with the clinicopathologic characteristics of GC. CREBRF silencing inhibited GC cell proliferation and induced G1/G0 to S phase cell cycle arrest through regulating Cyclin A, Cyclin D1 and CDK2 expressions. Furthermore, the results showed that knockdown of CREBRF suppressed the activation of AKT signaling pathway. We further discovered that activating of AKT rescued the effect of CREBRF silencing on cell growth and drove cell re-enter into the S phase of the cell cycle with SC79 (a AKT activator). Taken together, our study demonstrated that CREBRF might promote GC cell proliferation and induce G1-S phase transition through activating AKT signaling pathway. These findings suggest that CREBRF acts as a novel oncogene and may be a potential therapeutic target in therapy of GC.

Keywords

Gastric cancer CREBRF Proliferation Cell cycle AKT signaling pathway.

Han, J., Zhang, L., Zhang, J., Jiang, Q., Tong, D., Wang, X., Gao, X., Zhao, L., & Huang, C. (2018). CREBRF promotes the proliferation of human gastric cancer cells via the AKT signaling pathway. Cellular and Molecular Biology, 64(5), 40–45. https://doi.org/10.14715/cmb/2018.64.5.6

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References

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016; 66:7-30.
Chen W, Zheng R, Zuo T, Zeng H, Zhang S, He J. National cancer incidence and mortality in China, 2012. Chin J Cancer Res 2016; 28:1-11.
Li X, Li H, Zhang R, Liu J, Liu J. MicroRNA-449a inhibits proliferation and induces apoptosis by directly repressing E2F3 in gastric cancer. Cell Physiol Biochem 2015; 35:2033-2042.
Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang XS, et al. Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet 2015; 385:977-1010.
Zhang J, Tong DD, Xue M, Jiang QY, Wang XF, Yang PB, et al. FAM196B acts as oncogene and promotes proliferation of gastric cancer cells through AKTsignaling pathway. Cell Mol Biol (Noisy-le-grand) 2017; 63:18-23.
Zhao L, Liu Y, Tong D, Qin Y, Yang J, Xue M, et al. MeCP2 promotes gastric cancer progression through regulating FOXF1/Wnt5a/Î²-Catenin and MYOD1/Caspase-3 signaling pathways. EbioMedicine 2017; 16:87-100.
Zhao LY, Tong DD, Xue M, Ma HL, Liu SY, Yang J, et al. MeCP2, a target of miR-638, facilitates gastric cancer cell proliferation through activation of the MEK1/2-ERK1/2 signaling pathway by upregulating GIT1. Oncogenesis 2017; 6:e368.
Audas TE, Li Y, Liang G, Lu R. A novel protein, Luman/CREB3 recruitment factor, inhibits Luman activation of the unfolded protein response. Mol Cell Biol 2008; 28:3952-3966.
Mamdani F, Alda M, Grof P, Young LT, Rouleau G, Turecki G. Lithium response and genetic variation in the CREB family of genes. Am J Med Genet B Neuropsychiatr Genet 2008; 147B:500-504.
Mori K. Tripartite management of unfolded proteins in the endoplasmic reticulum. Cell 2000; 101:451-454.
Seok s, Fu T, Chois E, Li Y, Zhu R, Kumar S, et al. Transcriptional regulation of autophagy by an FXR-CREB axis. Nature 2014; 516:108-111.
Kim K, Chun KH, Suh PG, Kim IH. Alterations in cell proliferation related gene expressions in gastric cancer. Crit Rev Eukaryot Gene Expr 2011; 21:237-254.
Chaturvedi R, de Sablet T, Asim M, Piazuelo MB, Barry DP, Verriere TG et al. Increased Helicobacter pylori-associated gastric cancer risk in the Andean region of Colombia is mediated byspermine oxidase. Oncogene 2015; 34:3429-3440.
He L, Zhang Y, Sun H, Jiang F, Yang H, Wu H, et al. Targeting DNA flap endonuclease 1 to impede breast cancer progression. EbioMedicine 2016; 14:32-43.
Zhao R, Choi BY, Lee MH, Bode AM, Dong Z. Implications of genetic and epigenetic alterations of CDKN2A (p16(INK4a)) in cancer. EbioMedicine 2016; 8:30-39.
Yang Y, Jin Y, Martyn AC, Lin P, Song Y, Chen F, et al. Expression pattern implicates a potential role for luman recruitment factor in the process of implantation in uteri and development of preimplantation embryos in mice. J Reprod Dev 2013; 59:245-251.
Xue H, Yuan G, Guo X, Liu Q, Zhang J, Gao X, et al. A novel tumor-promoting mechanism of IL6 and the therapeutic efficacy of tocilizumab: Hypoxia-induced IL6 is a potent autophagy initiator in glioblastoma via the p-STAT3-MIR155-3p-CREBRF pathway. Autophagy 2016; 12:1129-1152.
Wang L, Yao J, Zhang X, Guo B, Le X, Cubberly M, et al. miRNA-302b suppresses human hepatocellular carcinoma by targeting AKT2. Mol Cancer Res 2014; 12:190-202.
Zhao LY, Yao Y, Han J, Yang J, Wang XF, Tong DD, et al. miR-638 suppresses cell proliferation in gastric cancer by targeting Sp2. Dig Dis Sci 2014; 59:1743-1753.
Chu X, Zhang T, Wang J, Li M, Zhang X, Tu J, et al. Alternative splicing variants of human Fbx4 disturb cyclin D1 proteolysis in human cancer. Biochem Biophys Res Commun 2014; 447:158-164.
Juengel E, Euler S, Maxeiner S, Rutz J, Justin S, Roos F, et al. Sulforaphane as an adjunctive to everolimus counteracts everolimus resistance in renal cancercell lines. Phytomedicine 2017; 27:1-7.
Hseu YC, Chao YH, Lin KY, Way TD, Lin HY, Thiyagarajan V, et al. Antrodia camphorata inhibits metastasis and epithelial"‘to"‘mesenchymal transition via the modulation of claudin"‘1 and Wnt/Î²"‘catenin signaling pathways in human colon cancer cells. J Ethnopharmacol 2017; 208:72–83.
Xu N, Lao Y, Zhang Y, Gillespie DA. AKT: a double-edged sword in cell proliferation and genome stability. J Oncol 2012; 2012:951724.
Chiappini PBO, de Medeiros IUD, Lima LGC, Fregnani JH, Nonogaki S, da Costa WL Jr, et al. Prognostic implications of phosphatidylinositol 3-kinase/AKT signaling pathway activation in gastric carcinomas. Arch Med Sci 2017; 13:1262-1268.
Maddika S, Ande SR, Wiechec E, Hansen LL, Wesselborg S, Los M. Akt-mediated phosphorylation of CDK2 regulates its dual role in cell cycle progression and apoptosis. J Cell Sci 2008; 121:979-988.
Zhang D, Zhang H, Hao S, Yan H, Zhang Z, Hu Y, et al. Akt specific activator SC79 protects against early brain injury following subarachnoid hemorrhage. ACS Chem Neurosci 2016; 7:710-718.

References

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016; 66:7-30.

Chen W, Zheng R, Zuo T, Zeng H, Zhang S, He J. National cancer incidence and mortality in China, 2012. Chin J Cancer Res 2016; 28:1-11.

Li X, Li H, Zhang R, Liu J, Liu J. MicroRNA-449a inhibits proliferation and induces apoptosis by directly repressing E2F3 in gastric cancer. Cell Physiol Biochem 2015; 35:2033-2042.

Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang XS, et al. Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet 2015; 385:977-1010.

Zhang J, Tong DD, Xue M, Jiang QY, Wang XF, Yang PB, et al. FAM196B acts as oncogene and promotes proliferation of gastric cancer cells through AKTsignaling pathway. Cell Mol Biol (Noisy-le-grand) 2017; 63:18-23.

Zhao L, Liu Y, Tong D, Qin Y, Yang J, Xue M, et al. MeCP2 promotes gastric cancer progression through regulating FOXF1/Wnt5a/Î²-Catenin and MYOD1/Caspase-3 signaling pathways. EbioMedicine 2017; 16:87-100.

Zhao LY, Tong DD, Xue M, Ma HL, Liu SY, Yang J, et al. MeCP2, a target of miR-638, facilitates gastric cancer cell proliferation through activation of the MEK1/2-ERK1/2 signaling pathway by upregulating GIT1. Oncogenesis 2017; 6:e368.

Audas TE, Li Y, Liang G, Lu R. A novel protein, Luman/CREB3 recruitment factor, inhibits Luman activation of the unfolded protein response. Mol Cell Biol 2008; 28:3952-3966.

Mamdani F, Alda M, Grof P, Young LT, Rouleau G, Turecki G. Lithium response and genetic variation in the CREB family of genes. Am J Med Genet B Neuropsychiatr Genet 2008; 147B:500-504.

Mori K. Tripartite management of unfolded proteins in the endoplasmic reticulum. Cell 2000; 101:451-454.

Seok s, Fu T, Chois E, Li Y, Zhu R, Kumar S, et al. Transcriptional regulation of autophagy by an FXR-CREB axis. Nature 2014; 516:108-111.

Kim K, Chun KH, Suh PG, Kim IH. Alterations in cell proliferation related gene expressions in gastric cancer. Crit Rev Eukaryot Gene Expr 2011; 21:237-254.

Chaturvedi R, de Sablet T, Asim M, Piazuelo MB, Barry DP, Verriere TG et al. Increased Helicobacter pylori-associated gastric cancer risk in the Andean region of Colombia is mediated byspermine oxidase. Oncogene 2015; 34:3429-3440.

He L, Zhang Y, Sun H, Jiang F, Yang H, Wu H, et al. Targeting DNA flap endonuclease 1 to impede breast cancer progression. EbioMedicine 2016; 14:32-43.

Zhao R, Choi BY, Lee MH, Bode AM, Dong Z. Implications of genetic and epigenetic alterations of CDKN2A (p16(INK4a)) in cancer. EbioMedicine 2016; 8:30-39.

Yang Y, Jin Y, Martyn AC, Lin P, Song Y, Chen F, et al. Expression pattern implicates a potential role for luman recruitment factor in the process of implantation in uteri and development of preimplantation embryos in mice. J Reprod Dev 2013; 59:245-251.

Xue H, Yuan G, Guo X, Liu Q, Zhang J, Gao X, et al. A novel tumor-promoting mechanism of IL6 and the therapeutic efficacy of tocilizumab: Hypoxia-induced IL6 is a potent autophagy initiator in glioblastoma via the p-STAT3-MIR155-3p-CREBRF pathway. Autophagy 2016; 12:1129-1152.

Wang L, Yao J, Zhang X, Guo B, Le X, Cubberly M, et al. miRNA-302b suppresses human hepatocellular carcinoma by targeting AKT2. Mol Cancer Res 2014; 12:190-202.

Zhao LY, Yao Y, Han J, Yang J, Wang XF, Tong DD, et al. miR-638 suppresses cell proliferation in gastric cancer by targeting Sp2. Dig Dis Sci 2014; 59:1743-1753.

Chu X, Zhang T, Wang J, Li M, Zhang X, Tu J, et al. Alternative splicing variants of human Fbx4 disturb cyclin D1 proteolysis in human cancer. Biochem Biophys Res Commun 2014; 447:158-164.

Juengel E, Euler S, Maxeiner S, Rutz J, Justin S, Roos F, et al. Sulforaphane as an adjunctive to everolimus counteracts everolimus resistance in renal cancercell lines. Phytomedicine 2017; 27:1-7.

Hseu YC, Chao YH, Lin KY, Way TD, Lin HY, Thiyagarajan V, et al. Antrodia camphorata inhibits metastasis and epithelial"‘to"‘mesenchymal transition via the modulation of claudin"‘1 and Wnt/Î²"‘catenin signaling pathways in human colon cancer cells. J Ethnopharmacol 2017; 208:72–83.

Xu N, Lao Y, Zhang Y, Gillespie DA. AKT: a double-edged sword in cell proliferation and genome stability. J Oncol 2012; 2012:951724.

Chiappini PBO, de Medeiros IUD, Lima LGC, Fregnani JH, Nonogaki S, da Costa WL Jr, et al. Prognostic implications of phosphatidylinositol 3-kinase/AKT signaling pathway activation in gastric carcinomas. Arch Med Sci 2017; 13:1262-1268.

Maddika S, Ande SR, Wiechec E, Hansen LL, Wesselborg S, Los M. Akt-mediated phosphorylation of CDK2 regulates its dual role in cell cycle progression and apoptosis. J Cell Sci 2008; 121:979-988.

Zhang D, Zhang H, Hao S, Yan H, Zhang Z, Hu Y, et al. Akt specific activator SC79 protects against early brain injury following subarachnoid hemorrhage. ACS Chem Neurosci 2016; 7:710-718.

Author biographies is not available.