Skip to main content
Top
Published in: Cancer Cell International 1/2020

01-12-2020 | Breast Cancer | Primary research

Roles of eIF3m in the tumorigenesis of triple negative breast cancer

Authors: Wei Han, Cong Zhang, Chun-tao Shi, Xiao-jiao Gao, Ming-hui Zhou, Qi-xiang Shao, Xiao-jun Shen, Cheng-jiang Wu, Fang Cao, Yong-wei Hu, Jian-liang Yuan, Hou-zhong Ding, Qing-hua Wang, Hao-nan Wang

Published in: Cancer Cell International | Issue 1/2020

Login to get access

Abstract

Background

Without targets, triple negative breast cancer (TNBC) has the worst prognosis in all subtypes of breast cancer (BC). Recently, eukaryotic translation initiation factor 3 m (eIF3m) has been declared to be involved in the malignant progression of various neoplasms. The aim of this study is to explore biological functions of eIF3m in TNBC.

Methods

Multiple databases, including Oncomine, KM-plotter and so on, were performed to analyze prognosis and function of eIF3m in TNBC. After transfection of eIF3m-shRNA lentivirus, CCK-8, colony formation assay, cell cycle analysis, wound healing assay, transwell assays, mitochondrial membrane potential assay and cell apoptosis analysis were performed to explore the roles of eIF3m in TNBC cell bio-behaviors. In addition, western blotting was conducted to analyze the potential molecular mechanisms of eIF3m.

Results

In multiple databases, up-regulated eIF3m had lower overall survival, relapse-free survival and post progression survival in BC. EIF3m expression in TNBC was obviously higher than in non-TNBC or normal breast tissues. Its expression in TNBC was positively related to differentiation, lymph node invasion and distant metastasis. After knockdown of eIF3m, cell proliferation, migration, invasion and levels of mitochondrial membrane potential of MDA-MB-231 and MDA-MB-436 were all significantly suppressed, while apoptosis rates of them were obviously increased. In addition, eIF3m could regulate cell-cycle, epithelial–mesenchymal transition and apoptosis-related proteins. Combined with public databases and RT-qPCR, 14 genes were identified to be modulated by eIF3m in the development of TNBC.

Conclusions

eIF3m is an unfavorable indicator of TNBC, and plays a vital role in the process of TNBC tumorigenesis.
Appendix
Available only for authorised users
Literature
1.
go back to reference Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.CrossRefPubMed Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.CrossRefPubMed
2.
go back to reference He MY, Rancoule C, Rehailia-Blanchard A, et al. Radiotherapy in triple-negative breast cancer: current situation and upcoming strategies. Crit Rev Oncol Hematol. 2018;131:96–101.PubMedCrossRef He MY, Rancoule C, Rehailia-Blanchard A, et al. Radiotherapy in triple-negative breast cancer: current situation and upcoming strategies. Crit Rev Oncol Hematol. 2018;131:96–101.PubMedCrossRef
3.
go back to reference Odle TG. Precision medicine in breast cancer. Radiol Technol. 2017;88(4):401M–21M.PubMed Odle TG. Precision medicine in breast cancer. Radiol Technol. 2017;88(4):401M–21M.PubMed
4.
go back to reference Wang WJ, Lei YY, Mei JH, Wang CL. Recent progress in HER2 associated breast cancer. Asian Pac J Cancer Prev. 2015;16(7):2591–600.PubMedCrossRef Wang WJ, Lei YY, Mei JH, Wang CL. Recent progress in HER2 associated breast cancer. Asian Pac J Cancer Prev. 2015;16(7):2591–600.PubMedCrossRef
6.
go back to reference Sadato D, Ono T, Gotoh-Saito S, et al. Eukaryotic translation initiation factor 3 (eIF3) subunit e is essential for embryonic development and cell proliferation. FEBS Open Bio. 2018;8(8):1188–201.PubMedPubMedCentralCrossRef Sadato D, Ono T, Gotoh-Saito S, et al. Eukaryotic translation initiation factor 3 (eIF3) subunit e is essential for embryonic development and cell proliferation. FEBS Open Bio. 2018;8(8):1188–201.PubMedPubMedCentralCrossRef
7.
go back to reference Raabe K, Honys D, Michailidis C. The role of eukaryotic initiation factor 3 in plant translation regulation. Plant Physiol Biochem. 2019;145:75–83.PubMedCrossRef Raabe K, Honys D, Michailidis C. The role of eukaryotic initiation factor 3 in plant translation regulation. Plant Physiol Biochem. 2019;145:75–83.PubMedCrossRef
8.
go back to reference Cate JH. Human eIF3: from ‘blobology’ to biological insight. Philos Trans R Soc Lond B Biol Sci. 2017;372(1716):176.CrossRef Cate JH. Human eIF3: from ‘blobology’ to biological insight. Philos Trans R Soc Lond B Biol Sci. 2017;372(1716):176.CrossRef
9.
go back to reference Yang C, Zhang Y, Du W, Cheng H, Li C. Eukaryotic translation initiation factor 3 subunit G promotes human colorectal cancer. Am J Transl Res. 2019;11(2):612–23.PubMedPubMedCentral Yang C, Zhang Y, Du W, Cheng H, Li C. Eukaryotic translation initiation factor 3 subunit G promotes human colorectal cancer. Am J Transl Res. 2019;11(2):612–23.PubMedPubMedCentral
10.
go back to reference Wang X, Wang H, Zhao S, et al. Eukaryotic translation initiation factor EIF3H potentiates gastric carcinoma cell proliferation. Tissue Cell. 2018;53:23–9.PubMedCrossRef Wang X, Wang H, Zhao S, et al. Eukaryotic translation initiation factor EIF3H potentiates gastric carcinoma cell proliferation. Tissue Cell. 2018;53:23–9.PubMedCrossRef
11.
go back to reference Zhao W, Li X, Wang J, et al. Decreasing eukaryotic initiation factor 3C (EIF3C) suppresses proliferation and stimulates apoptosis in breast cancer cell lines through mammalian target of rapamycin (mTOR) pathway. Med Sci Monit. 2017;23:4182–91.PubMedPubMedCentralCrossRef Zhao W, Li X, Wang J, et al. Decreasing eukaryotic initiation factor 3C (EIF3C) suppresses proliferation and stimulates apoptosis in breast cancer cell lines through mammalian target of rapamycin (mTOR) pathway. Med Sci Monit. 2017;23:4182–91.PubMedPubMedCentralCrossRef
12.
go back to reference Zeng L, Wan Y, Li D, et al. The m subunit of murine translation initiation factor eIF3 maintains the integrity of the eIF3 complex and is required for embryonic development, homeostasis, and organ size control. J Biol Chem. 2013;288(42):30087–93.PubMedPubMedCentralCrossRef Zeng L, Wan Y, Li D, et al. The m subunit of murine translation initiation factor eIF3 maintains the integrity of the eIF3 complex and is required for embryonic development, homeostasis, and organ size control. J Biol Chem. 2013;288(42):30087–93.PubMedPubMedCentralCrossRef
13.
go back to reference Goh SH, Hong SH, Hong SH, et al. eIF3m expression influences the regulation of tumorigenesis-related genes in human colon cancer. Oncogene. 2011;30(4):398–409.PubMedCrossRef Goh SH, Hong SH, Hong SH, et al. eIF3m expression influences the regulation of tumorigenesis-related genes in human colon cancer. Oncogene. 2011;30(4):398–409.PubMedCrossRef
14.
go back to reference Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25(4):402–8.PubMedCrossRef Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25(4):402–8.PubMedCrossRef
15.
16.
18.
go back to reference Xiong Y, Deng Y, Wang K, et al. Profiles of alternative splicing in colorectal cancer and their clinical significance: a study based on large-scale sequencing data. EBioMedicine. 2018;36:183–95.PubMedPubMedCentralCrossRef Xiong Y, Deng Y, Wang K, et al. Profiles of alternative splicing in colorectal cancer and their clinical significance: a study based on large-scale sequencing data. EBioMedicine. 2018;36:183–95.PubMedPubMedCentralCrossRef
19.
go back to reference Stahl S, Silva MateusSeidl AR, Ducret A, et al. Loss of diphthamide pre-activates NF-κB and death receptor pathways and renders MCF7 cells hypersensitive to tumor necrosis factor. Proc Natl Acad Sci U S A. 2015;112(34):10732–7.PubMedPubMedCentralCrossRef Stahl S, Silva MateusSeidl AR, Ducret A, et al. Loss of diphthamide pre-activates NF-κB and death receptor pathways and renders MCF7 cells hypersensitive to tumor necrosis factor. Proc Natl Acad Sci U S A. 2015;112(34):10732–7.PubMedPubMedCentralCrossRef
20.
go back to reference Hong SH, Lee WJ, Kim YD, et al. APIP, an ERBB3-binding partner, stimulates erbB2-3 heterodimer formation to promote tumorigenesis. Oncotarget. 2016;7(16):21601–17.PubMedPubMedCentralCrossRef Hong SH, Lee WJ, Kim YD, et al. APIP, an ERBB3-binding partner, stimulates erbB2-3 heterodimer formation to promote tumorigenesis. Oncotarget. 2016;7(16):21601–17.PubMedPubMedCentralCrossRef
21.
go back to reference Gong B, Hu H, Chen J, et al. Caprin-1 is a novel microRNA-223 target for regulating the proliferation and invasion of human breast cancer cells. Biomed Pharmacother. 2013;67(7):629–36.PubMedCrossRef Gong B, Hu H, Chen J, et al. Caprin-1 is a novel microRNA-223 target for regulating the proliferation and invasion of human breast cancer cells. Biomed Pharmacother. 2013;67(7):629–36.PubMedCrossRef
22.
23.
go back to reference Wu J, Zhu H, Wu J, et al. Inhibition of N-acetyltransferase 10 using remodelin attenuates doxorubicin resistance by reversing the epithelial-mesenchymal transition in breast cancer. Am J Transl Res. 2018;10(1):256–64.PubMedPubMedCentral Wu J, Zhu H, Wu J, et al. Inhibition of N-acetyltransferase 10 using remodelin attenuates doxorubicin resistance by reversing the epithelial-mesenchymal transition in breast cancer. Am J Transl Res. 2018;10(1):256–64.PubMedPubMedCentral
24.
go back to reference Peter CJ, Saito A, Hasegawa Y, et al. In vivo epigenetic editing of Sema6a promoter reverses transcallosal dysconnectivity caused by C11orf46/Arl14ep risk gene. Nat Commun. 2019;10(1):4112.PubMedPubMedCentralCrossRef Peter CJ, Saito A, Hasegawa Y, et al. In vivo epigenetic editing of Sema6a promoter reverses transcallosal dysconnectivity caused by C11orf46/Arl14ep risk gene. Nat Commun. 2019;10(1):4112.PubMedPubMedCentralCrossRef
25.
go back to reference Voisin S, Almén MS, Zheleznyakova GY, et al. Many obesity-associated SNPs strongly associate with DNA methylation changes at proximal promoters and enhancers. Genome Med. 2015;7:103.PubMedPubMedCentralCrossRef Voisin S, Almén MS, Zheleznyakova GY, et al. Many obesity-associated SNPs strongly associate with DNA methylation changes at proximal promoters and enhancers. Genome Med. 2015;7:103.PubMedPubMedCentralCrossRef
26.
go back to reference Xu Y, Zhou W, Ji Y, et al. Elongator promotes the migration and invasion of hepatocellular carcinoma cell by the phosphorylation of AKT. Int J Biol Sci. 2018;14(5):518–30.PubMedPubMedCentralCrossRef Xu Y, Zhou W, Ji Y, et al. Elongator promotes the migration and invasion of hepatocellular carcinoma cell by the phosphorylation of AKT. Int J Biol Sci. 2018;14(5):518–30.PubMedPubMedCentralCrossRef
27.
go back to reference Isogai T, van der Kammen R, Goerdayal SS, et al. Proteomic analyses uncover a new function and mode of action for mouse homolog of Diaphanous 2 (mDia2). Mol Cell Proteomics. 2015;14(4):1064–78.PubMedPubMedCentralCrossRef Isogai T, van der Kammen R, Goerdayal SS, et al. Proteomic analyses uncover a new function and mode of action for mouse homolog of Diaphanous 2 (mDia2). Mol Cell Proteomics. 2015;14(4):1064–78.PubMedPubMedCentralCrossRef
28.
go back to reference Zhan W, Wang W, Han T, et al. COMMD9 promotes TFDP1/E2F1 transcriptional activity via interaction with TFDP1 in non-small cell lung cancer. Cell Signal. 2017;30:59–66.PubMedCrossRef Zhan W, Wang W, Han T, et al. COMMD9 promotes TFDP1/E2F1 transcriptional activity via interaction with TFDP1 in non-small cell lung cancer. Cell Signal. 2017;30:59–66.PubMedCrossRef
29.
go back to reference Basset C, Bonnet-Magnaval F, Navarro MG, et al. Api5 a new cofactor of estrogen receptor alpha involved in breast cancer outcome. Oncotarget. 2017;8(32):52511–26.PubMedPubMedCentralCrossRef Basset C, Bonnet-Magnaval F, Navarro MG, et al. Api5 a new cofactor of estrogen receptor alpha involved in breast cancer outcome. Oncotarget. 2017;8(32):52511–26.PubMedPubMedCentralCrossRef
30.
go back to reference Zhou Z, Liu Y, Ma M, Chang L. Knockdown of TRIM44 inhibits the proliferation and invasion in papillary thyroid cancer cells through suppressing the Wnt/β-catenin signaling pathway. Biomed Pharmacother. 2017;96:98–103.PubMedCrossRef Zhou Z, Liu Y, Ma M, Chang L. Knockdown of TRIM44 inhibits the proliferation and invasion in papillary thyroid cancer cells through suppressing the Wnt/β-catenin signaling pathway. Biomed Pharmacother. 2017;96:98–103.PubMedCrossRef
31.
go back to reference Yu J, Qin B, Moyer AM, et al. DNA methyltransferase expression in triple-negative breast cancer predicts sensitivity to decitabine. J Clin Invest. 2018;128(6):2376–88.PubMedPubMedCentralCrossRef Yu J, Qin B, Moyer AM, et al. DNA methyltransferase expression in triple-negative breast cancer predicts sensitivity to decitabine. J Clin Invest. 2018;128(6):2376–88.PubMedPubMedCentralCrossRef
32.
go back to reference Geng W, Liang W, Fan Y, Ye Z, Zhang L. Overexpression of CCDC34 in colorectal cancer and its involvement in tumor growth, apoptosis and invasion. Mol Med Rep. 2018;17(1):465–73.PubMed Geng W, Liang W, Fan Y, Ye Z, Zhang L. Overexpression of CCDC34 in colorectal cancer and its involvement in tumor growth, apoptosis and invasion. Mol Med Rep. 2018;17(1):465–73.PubMed
33.
go back to reference Takahara M, Kunii M, Nakamura K, et al. C11ORF74 interacts with the IFT-A complex and participates in ciliary BBSome localization. J Biochem. 2019;165(3):257–67.PubMedCrossRef Takahara M, Kunii M, Nakamura K, et al. C11ORF74 interacts with the IFT-A complex and participates in ciliary BBSome localization. J Biochem. 2019;165(3):257–67.PubMedCrossRef
34.
go back to reference Shimozono N, Jinnin M, Masuzawa M, et al. NUP160-SLC43A3 is a novel recurrent fusion oncogene in angiosarcoma. Cancer Res. 2015;75(21):4458–65.PubMedCrossRef Shimozono N, Jinnin M, Masuzawa M, et al. NUP160-SLC43A3 is a novel recurrent fusion oncogene in angiosarcoma. Cancer Res. 2015;75(21):4458–65.PubMedCrossRef
35.
go back to reference Seabra CM, Quental S, Neto AP, et al. A novel Alu-mediated microdeletion at 11p13 removes WT1 in a patient with cryptorchidism and azoospermia. Reprod Biomed Online. 2014;29(3):388–91.PubMedCrossRef Seabra CM, Quental S, Neto AP, et al. A novel Alu-mediated microdeletion at 11p13 removes WT1 in a patient with cryptorchidism and azoospermia. Reprod Biomed Online. 2014;29(3):388–91.PubMedCrossRef
38.
go back to reference Dong Z, Zhang JT. Initiation factor eIF3 and regulation of mRNA translation, cell growth, and cancer. Crit Rev Oncol Hematol. 2006;59(3):169–80.PubMedCrossRef Dong Z, Zhang JT. Initiation factor eIF3 and regulation of mRNA translation, cell growth, and cancer. Crit Rev Oncol Hematol. 2006;59(3):169–80.PubMedCrossRef
39.
go back to reference Yin JY, Dong Z, Liu ZQ, Zhang JT. Translational control gone awry: a new mechanism of tumorigenesis and novel targets of cancer treatments. Biosci Rep. 2011;31(1):1–15.PubMedCrossRef Yin JY, Dong Z, Liu ZQ, Zhang JT. Translational control gone awry: a new mechanism of tumorigenesis and novel targets of cancer treatments. Biosci Rep. 2011;31(1):1–15.PubMedCrossRef
40.
go back to reference Devanand P, Sundaramoorthy S, Ryu MS, Jayabalan AK, Ohn T, Lim IK. Translational downregulation of Twist1 expression by antiproliferative gene, B-cell translocation gene 2, in the triple negative breast cancer cells. Cell Death Dis. 2019;10(6):410.PubMedPubMedCentralCrossRef Devanand P, Sundaramoorthy S, Ryu MS, Jayabalan AK, Ohn T, Lim IK. Translational downregulation of Twist1 expression by antiproliferative gene, B-cell translocation gene 2, in the triple negative breast cancer cells. Cell Death Dis. 2019;10(6):410.PubMedPubMedCentralCrossRef
41.
go back to reference Zheng Q, Liu H, Ye J, et al. Nuclear distribution of eIF3g and its interacting nuclear proteins in breast cancer cells. Mol Med Rep. 2016;13(4):2973–80.PubMedPubMedCentralCrossRef Zheng Q, Liu H, Ye J, et al. Nuclear distribution of eIF3g and its interacting nuclear proteins in breast cancer cells. Mol Med Rep. 2016;13(4):2973–80.PubMedPubMedCentralCrossRef
42.
go back to reference Fang HY, Chen SB, Guo DJ, Pan SY, Yu ZL. Proteomic identification of differentially expressed proteins in curcumin-treated MCF-7 cells. Phytomedicine. 2011;18(8–9):697–703.PubMedCrossRef Fang HY, Chen SB, Guo DJ, Pan SY, Yu ZL. Proteomic identification of differentially expressed proteins in curcumin-treated MCF-7 cells. Phytomedicine. 2011;18(8–9):697–703.PubMedCrossRef
43.
go back to reference Ma F, Li X, Ren J, et al. Downregulation of eukaryotic translation initiation factor 3b inhibited proliferation and metastasis of gastric cancer. Cell Death Dis. 2019;10(9):623.PubMedPubMedCentralCrossRef Ma F, Li X, Ren J, et al. Downregulation of eukaryotic translation initiation factor 3b inhibited proliferation and metastasis of gastric cancer. Cell Death Dis. 2019;10(9):623.PubMedPubMedCentralCrossRef
44.
go back to reference Fan Y, Guo Y. Knockdown of eIF3D inhibits breast cancer cell proliferation and invasion through suppressing the Wnt/β-catenin signaling pathway. Int J Clin Exp Pathol. 2015;8(9):10420–7.PubMedPubMedCentral Fan Y, Guo Y. Knockdown of eIF3D inhibits breast cancer cell proliferation and invasion through suppressing the Wnt/β-catenin signaling pathway. Int J Clin Exp Pathol. 2015;8(9):10420–7.PubMedPubMedCentral
45.
go back to reference Grzmil M, Rzymski T, Milani M, et al. An oncogenic role of eIF3e/INT6 in human breast cancer. Oncogene. 2010;29(28):4080–9.PubMedCrossRef Grzmil M, Rzymski T, Milani M, et al. An oncogenic role of eIF3e/INT6 in human breast cancer. Oncogene. 2010;29(28):4080–9.PubMedCrossRef
46.
go back to reference Cuesta R, Berman AY, Alayev A, et al. Estrogen receptor α promotes protein synthesis by fine-tuning the expression of the eukaryotic translation initiation factor 3 subunit f (eIF3f). J Biol Chem. 2019;294(7):2267–78.PubMedCrossRef Cuesta R, Berman AY, Alayev A, et al. Estrogen receptor α promotes protein synthesis by fine-tuning the expression of the eukaryotic translation initiation factor 3 subunit f (eIF3f). J Biol Chem. 2019;294(7):2267–78.PubMedCrossRef
48.
go back to reference Van Tongelen A, Loriot A, De Smet C. Oncogenic roles of DNA hypomethylation through the activation of cancer-germline genes. Cancer Lett. 2017;396:130–7.PubMedCrossRef Van Tongelen A, Loriot A, De Smet C. Oncogenic roles of DNA hypomethylation through the activation of cancer-germline genes. Cancer Lett. 2017;396:130–7.PubMedCrossRef
Metadata
Title
Roles of eIF3m in the tumorigenesis of triple negative breast cancer
Authors
Wei Han
Cong Zhang
Chun-tao Shi
Xiao-jiao Gao
Ming-hui Zhou
Qi-xiang Shao
Xiao-jun Shen
Cheng-jiang Wu
Fang Cao
Yong-wei Hu
Jian-liang Yuan
Hou-zhong Ding
Qing-hua Wang
Hao-nan Wang
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01220-z

Other articles of this Issue 1/2020

Cancer Cell International 1/2020 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