Skip to main content
Top
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | Primary research

TRIM27 promotes the development of esophagus cancer via regulating PTEN/AKT signaling pathway

Authors: Liang Ma, Ninghua Yao, Ping Chen, Zhixiang Zhuang

Published in: Cancer Cell International | Issue 1/2019

Login to get access

Abstract

Background

Tripartite motif‑containing 27 (TRIM27) belongs to the TRIM protein family, which is closely related to the progression of some certain human cancers. Nevertheless, the biological function of TRIM27 in esophageal squamous cell carcinoma (ESCC) is still not clear. The aim of present research is to examine the function of TRIM27 in ESCC cells.

Methods

In the present study, RNA interference (RNAi) and lentiviral vector were used to knockdown and overexpression of TRIM27 in ESCC cells respectively. qRT-PCR and western blot were used to examine the expression of TRIM27 in ESCC cells. Cell counting kit-8 (CCK-8) assay was performed to determine the proliferation of cells.

Results

Our analyses indicated that TRIM27 was a pro-proliferation factor in ESCC cells. Moreover, overexpression of TRIM27 deeply suppressed the apoptosis of ESCC cells and accelerated its glucose uptake. In addition, an AKT inhibitor LY294002 was used to determine the connection between TRIM27 and AKT in ESCC cells. Our results demonstrated that TRIM27 has involved in the PI3/AKT signaling pathway. Moreover, TRIM27 interacted with PTEN and mediated its poly-ubiquitination in ESCC cells. Importantly, the glycolysis inhibitor 3-BrPA also inhibited the effect of TRIM27 on ESCC cells. Hence, TRIM27 also participated in the regulation of energy metabolism in ESCC cells.

Conclusions

This research not only gained a deep insight into the biological function of TRIM27 but also elucidated its potential target and signaling pathway in human ESCC cells.
Appendix
Available only for authorised users
Literature
1.
go back to reference Cristina B, Fabio L, Jacques F, Werner G, Franca L, Paola B, Eva N, Carlo LV. Trends in oesophageal cancer incidence and mortality in Europe. Int J Cancer. 2010;122(5):1118–29. Cristina B, Fabio L, Jacques F, Werner G, Franca L, Paola B, Eva N, Carlo LV. Trends in oesophageal cancer incidence and mortality in Europe. Int J Cancer. 2010;122(5):1118–29.
2.
go back to reference Siegel RL, Fedewa SA, Miller KD, Ann GS, Pinheiro PS, Dinorah MT, Ahmedin J. Cancer statistics for Hispanics/Latinos, 2015. CA Cancer J Clin. 2016;65(6):457–80.CrossRef Siegel RL, Fedewa SA, Miller KD, Ann GS, Pinheiro PS, Dinorah MT, Ahmedin J. Cancer statistics for Hispanics/Latinos, 2015. CA Cancer J Clin. 2016;65(6):457–80.CrossRef
3.
go back to reference di Pietro M, Canto MI, Fitzgerald RC. Endoscopic management of early adenocarcinoma and squamous cell carcinoma of the esophagus: screening, diagnosis, and therapy. Gastroenterology. 2018;154(2):421–36.PubMedCrossRef di Pietro M, Canto MI, Fitzgerald RC. Endoscopic management of early adenocarcinoma and squamous cell carcinoma of the esophagus: screening, diagnosis, and therapy. Gastroenterology. 2018;154(2):421–36.PubMedCrossRef
4.
go back to reference Micale L, Chaignat E, Fusco C, Reymond A, Merla G. The tripartite motif: structure and function. Adv Exp Med Biol. 2012;770:11–25.PubMedCrossRef Micale L, Chaignat E, Fusco C, Reymond A, Merla G. The tripartite motif: structure and function. Adv Exp Med Biol. 2012;770:11–25.PubMedCrossRef
5.
go back to reference Zhang Y, Feng Y, Ji D, Wang Q, Qian W, Wang S, Zhang Z, Ji B, Zhang C, Sun Y, et al. TRIM27 functions as an oncogene by activating epithelial–mesenchymal transition and p-AKT in colorectal cancer. Int J Oncol. 2018;53:620–32.PubMedPubMedCentral Zhang Y, Feng Y, Ji D, Wang Q, Qian W, Wang S, Zhang Z, Ji B, Zhang C, Sun Y, et al. TRIM27 functions as an oncogene by activating epithelial–mesenchymal transition and p-AKT in colorectal cancer. Int J Oncol. 2018;53:620–32.PubMedPubMedCentral
6.
go back to reference Ma Y, Wei Z, Bast RC Jr, Wang Z, Li Y, Gao M, Liu Y, Wang X, Guo C, Zhang L, et al. Downregulation of TRIM27 expression inhibits the proliferation of ovarian cancer cells in vitro and in vivo. Lab Invest. 2016;96(1):37–48.PubMedCrossRef Ma Y, Wei Z, Bast RC Jr, Wang Z, Li Y, Gao M, Liu Y, Wang X, Guo C, Zhang L, et al. Downregulation of TRIM27 expression inhibits the proliferation of ovarian cancer cells in vitro and in vivo. Lab Invest. 2016;96(1):37–48.PubMedCrossRef
7.
go back to reference Meng YY, Wang X, Huang DD, Jin QZ, Chen WB, Cai ZY. Knockdown of TRIM27 expression regulates cell proliferation, invasion and migration in human nasopharyngeal 5-8F carcinoma cells. Chin J Pathophysiol. 2017;33(01):53–9. Meng YY, Wang X, Huang DD, Jin QZ, Chen WB, Cai ZY. Knockdown of TRIM27 expression regulates cell proliferation, invasion and migration in human nasopharyngeal 5-8F carcinoma cells. Chin J Pathophysiol. 2017;33(01):53–9.
8.
go back to reference Mohammad Mahabub-Uz Z, Teruaki N, Tsuyoshi T, Tomoo O, Wanzhu J, Toshie S, Yasunori T, Shunsuke I. Ubiquitination-deubiquitination by the TRIM27–USP7 complex regulates tumor necrosis factor alpha-induced apoptosis. Mol Cell Biol. 2013;33(24):4971–84.CrossRef Mohammad Mahabub-Uz Z, Teruaki N, Tsuyoshi T, Tomoo O, Wanzhu J, Toshie S, Yasunori T, Shunsuke I. Ubiquitination-deubiquitination by the TRIM27–USP7 complex regulates tumor necrosis factor alpha-induced apoptosis. Mol Cell Biol. 2013;33(24):4971–84.CrossRef
9.
go back to reference Fang-Fang S, Wen-Bin Y, Fu-You Z, Ying P, Xue-Ke Z, Yan J, Xin S, Bei L, Xue-Na H, Sa T. Variations in the MHC region confer risk to esophageal squamous cell carcinoma on the subjects from high-incidence area in northern China. PLoS ONE. 2014;9(3):e90438.CrossRef Fang-Fang S, Wen-Bin Y, Fu-You Z, Ying P, Xue-Ke Z, Yan J, Xin S, Bei L, Xue-Na H, Sa T. Variations in the MHC region confer risk to esophageal squamous cell carcinoma on the subjects from high-incidence area in northern China. PLoS ONE. 2014;9(3):e90438.CrossRef
10.
go back to reference Wang Q, Chen X, Hay N. Akt as a target for cancer therapy: more is not always better (lessons from studies in mice). Br J Cancer. 2017;117(2):159–63.PubMedPubMedCentralCrossRef Wang Q, Chen X, Hay N. Akt as a target for cancer therapy: more is not always better (lessons from studies in mice). Br J Cancer. 2017;117(2):159–63.PubMedPubMedCentralCrossRef
11.
go back to reference Sun Y, Ji B, Feng Y, Zhang Y, Ji D, Zhu C, Wang S, Zhang C, Zhang D, Sun Y. TRIM59 facilitates the proliferation of colorectal cancer and promotes metastasis via the PI3K/AKT pathway. Oncol Rep. 2017;38(1):43–52.PubMedPubMedCentralCrossRef Sun Y, Ji B, Feng Y, Zhang Y, Ji D, Zhu C, Wang S, Zhang C, Zhang D, Sun Y. TRIM59 facilitates the proliferation of colorectal cancer and promotes metastasis via the PI3K/AKT pathway. Oncol Rep. 2017;38(1):43–52.PubMedPubMedCentralCrossRef
12.
go back to reference Xu G, Guo Y, Xu D, Wang Y, Shen Y, Wang F, Lv Y, Song F, Jiang D, Zhang Y. TRIM14 regulates cell proliferation and invasion in osteosarcoma via promotion of the AKT signaling pathway. Sci Rep. 2017;7:42411.PubMedPubMedCentralCrossRef Xu G, Guo Y, Xu D, Wang Y, Shen Y, Wang F, Lv Y, Song F, Jiang D, Zhang Y. TRIM14 regulates cell proliferation and invasion in osteosarcoma via promotion of the AKT signaling pathway. Sci Rep. 2017;7:42411.PubMedPubMedCentralCrossRef
13.
go back to reference He D, Zhang S. UNBS5162 inhibits the proliferation of esophageal cancer squamous cells via the PI3K/AKT signaling pathway. Mol Med Rep. 2017;17(1):549–55.PubMed He D, Zhang S. UNBS5162 inhibits the proliferation of esophageal cancer squamous cells via the PI3K/AKT signaling pathway. Mol Med Rep. 2017;17(1):549–55.PubMed
14.
go back to reference Li B, Wen WX, Lam AKY, Yang W, Hu HF, Xin YG, Yan RQ, Saremi N, Tsao SW, He QY. Significance of PI3K/AKT signaling pathway in metastasis of esophageal squamous cell carcinoma and its potential as a target for anti-metastasis therapy. Oncotarget. 2017;8(24):38755–66.PubMedPubMedCentral Li B, Wen WX, Lam AKY, Yang W, Hu HF, Xin YG, Yan RQ, Saremi N, Tsao SW, He QY. Significance of PI3K/AKT signaling pathway in metastasis of esophageal squamous cell carcinoma and its potential as a target for anti-metastasis therapy. Oncotarget. 2017;8(24):38755–66.PubMedPubMedCentral
15.
16.
go back to reference Lu YX, Wu QN, Chen DL, Chen LZ, Wang ZX, Ren C, Mo HY, Chen Y, Sheng H, Wang YN, et al. Pharmacological ascorbate suppresses growth of gastric cancer cells with GLUT1 overexpression and enhances the efficacy of oxaliplatin through redox modulation. Theranostics. 2018;8(5):1312–26.PubMedPubMedCentralCrossRef Lu YX, Wu QN, Chen DL, Chen LZ, Wang ZX, Ren C, Mo HY, Chen Y, Sheng H, Wang YN, et al. Pharmacological ascorbate suppresses growth of gastric cancer cells with GLUT1 overexpression and enhances the efficacy of oxaliplatin through redox modulation. Theranostics. 2018;8(5):1312–26.PubMedPubMedCentralCrossRef
18.
go back to reference Liu Y, Murray-Stewart T, Casero RA Jr, Kagiampakis I, Jin L, Zhang J, Wang H, Che Q, Tong H, Ke J, et al. Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth. Int J Oncol. 2017;50(6):2011–23.PubMedPubMedCentralCrossRef Liu Y, Murray-Stewart T, Casero RA Jr, Kagiampakis I, Jin L, Zhang J, Wang H, Che Q, Tong H, Ke J, et al. Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth. Int J Oncol. 2017;50(6):2011–23.PubMedPubMedCentralCrossRef
20.
go back to reference Joshi A, Ellenson LH. PI3K/PTEN/AKT genetic mouse models of endometrial carcinoma. Adv Exp Med Biol. 2017;943:261–73.PubMedCrossRef Joshi A, Ellenson LH. PI3K/PTEN/AKT genetic mouse models of endometrial carcinoma. Adv Exp Med Biol. 2017;943:261–73.PubMedCrossRef
21.
go back to reference Zhang S, Zhang Y, Qu J, Che X, Fan Y, Hou K, Guo T, Deng G, Song N, Li C. Exosomes promote cetuximab resistance via the PTEN/Akt pathway in colon cancer cells. Braz J Med Biol Res. 2018;51(1):e6472.CrossRef Zhang S, Zhang Y, Qu J, Che X, Fan Y, Hou K, Guo T, Deng G, Song N, Li C. Exosomes promote cetuximab resistance via the PTEN/Akt pathway in colon cancer cells. Braz J Med Biol Res. 2018;51(1):e6472.CrossRef
23.
go back to reference Lee JT, Jing S, Jiayun Z, Muyang L, Brenda Z, Amanda Z, Ramon P, Wei G. RFP-mediated ubiquitination of PTEN modulates its effect on AKT activation. Cell Res. 2013;23(4):552–64.PubMedPubMedCentralCrossRef Lee JT, Jing S, Jiayun Z, Muyang L, Brenda Z, Amanda Z, Ramon P, Wei G. RFP-mediated ubiquitination of PTEN modulates its effect on AKT activation. Cell Res. 2013;23(4):552–64.PubMedPubMedCentralCrossRef
24.
25.
go back to reference Hatakeyama S. TRIM family proteins: roles in autophagy, immunity, and carcinogenesis. Trends Biochem Sci. 2017;42(4):297.PubMedCrossRef Hatakeyama S. TRIM family proteins: roles in autophagy, immunity, and carcinogenesis. Trends Biochem Sci. 2017;42(4):297.PubMedCrossRef
27.
go back to reference Miriam M, Maria Chiara DS, Laura B, Federico G, Emilio H. PI3K/AKT signaling pathway and cancer: an updated review. Ann Med. 2014;46(6):372–83.CrossRef Miriam M, Maria Chiara DS, Laura B, Federico G, Emilio H. PI3K/AKT signaling pathway and cancer: an updated review. Ann Med. 2014;46(6):372–83.CrossRef
28.
go back to reference Jia M, Chen X, Liu J, Chen J. PTEN promotes apoptosis of H2O2-injured rat nasal epithelial cells through PI3K/Akt and other pathways. Mol Med Rep. 2017;17(1):571.PubMed Jia M, Chen X, Liu J, Chen J. PTEN promotes apoptosis of H2O2-injured rat nasal epithelial cells through PI3K/Akt and other pathways. Mol Med Rep. 2017;17(1):571.PubMed
29.
go back to reference Gill KS, Fernandes P, Donovan TR, Mckenna SL, Doddakula KK, Power DG, Soden DM, Forde PF. Glycolysis inhibition as a cancer treatment and its role in an anti-tumour immune response. Biochim Biophys Acta. 2016;1866(1):87–105.PubMed Gill KS, Fernandes P, Donovan TR, Mckenna SL, Doddakula KK, Power DG, Soden DM, Forde PF. Glycolysis inhibition as a cancer treatment and its role in an anti-tumour immune response. Biochim Biophys Acta. 2016;1866(1):87–105.PubMed
30.
go back to reference Ryu MJ, Han J, Kim SJ, Lee MJ, Ju X, Lee YL, Son JH, Cui J, Jang Y, Chung W, Song IC, Kweon GR, Heo JY. PTEN/AKT signaling mediates chemoresistance in refractory acute myeloid leukemia through enhanced glycolysis. Oncol Rep. 2019;42(5):2149–58.PubMed Ryu MJ, Han J, Kim SJ, Lee MJ, Ju X, Lee YL, Son JH, Cui J, Jang Y, Chung W, Song IC, Kweon GR, Heo JY. PTEN/AKT signaling mediates chemoresistance in refractory acute myeloid leukemia through enhanced glycolysis. Oncol Rep. 2019;42(5):2149–58.PubMed
31.
go back to reference Fenglin C, Mingkai Z, Canmei Z, Jun P, Xiaozhong W, Jianying L, Zhixin C, Yuehong H. Baicalein reverses hypoxia-induced 5-FU resistance in gastric cancer AGS cells through suppression of glycolysis and the PTEN/Akt/HIF-1α signaling pathway. Oncol Rep. 2015;33(1):457–63.CrossRef Fenglin C, Mingkai Z, Canmei Z, Jun P, Xiaozhong W, Jianying L, Zhixin C, Yuehong H. Baicalein reverses hypoxia-induced 5-FU resistance in gastric cancer AGS cells through suppression of glycolysis and the PTEN/Akt/HIF-1α signaling pathway. Oncol Rep. 2015;33(1):457–63.CrossRef
32.
go back to reference Blouin MJ, Zhao Y, Zakikhani M, Algire C, Piura E, Pollak M. Loss of function of PTEN alters the relationship between glucose concentration and cell proliferation, increases glycolysis, and sensitizes cells to 2-deoxyglucose. Cancer Lett. 2010;289(2):246–53.PubMedCrossRef Blouin MJ, Zhao Y, Zakikhani M, Algire C, Piura E, Pollak M. Loss of function of PTEN alters the relationship between glucose concentration and cell proliferation, increases glycolysis, and sensitizes cells to 2-deoxyglucose. Cancer Lett. 2010;289(2):246–53.PubMedCrossRef
Metadata
Title
TRIM27 promotes the development of esophagus cancer via regulating PTEN/AKT signaling pathway
Authors
Liang Ma
Ninghua Yao
Ping Chen
Zhixiang Zhuang
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0998-4

Other articles of this Issue 1/2019

Cancer Cell International 1/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine