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Published in: Journal of Translational Medicine 1/2021

Open Access 01-12-2021 | Breast Cancer | Research

DEAD-box helicase 27 enhances stem cell-like properties with poor prognosis in breast cancer

Authors: Shan Li, Jinfei Ma, Ang Zheng, Xinyue Song, Si Chen, Feng Jin

Published in: Journal of Translational Medicine | Issue 1/2021

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Abstract

Background

Although the rapid development of diagnosis and treatment has improved prognosis in early breast cancer, challenges from different therapeutic response remain due to breast cancer heterogeneity. DEAD-box helicase 27 (DDX27) had been proved to influence ribosome biogenesis and identified as a promoter in gastric and colorectal cancer associated with stem cell-like properties, while the impact of DDX27 on breast cancer prognosis and biological functions is unclear. We aimed to explore the influence of DDX27 on stem cell-like properties and prognosis in breast cancer.

Methods

The expression of DDX27 was evaluated in 24 pairs of fresh breast cancer and normal tissue by western blot. We conducted Immunohistochemical (IHC) staining in paraffin sections of 165 breast cancer patients to analyze the expression of DDX27 and its correlation to stemness biomarker. The Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) database and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database were used to analyze the expression of DDX27 in breast cancer. Kaplan–Meier survival analysis were used to investigate the implication of DDX27 on breast cancer prognosis. Western blot, CCK-8 assay, Transwell assay and wound-healing assay were carried out to clarify the regulation of DDX27 on stem cell-like properties in breast cancer cells. Gene Set Enrichment Analysis (GSEA) was performed to analyze the potential molecular mechanisms of DDX27 in breast cancer.

Results

DDX27 was significantly high expressed in breast cancer compared with normal tissue. High expression of DDX27 was related to larger tumor size (p = 0.0005), positive lymph nodes (p = 0.0008), higher histological grade (p = 0.0040), higher ki-67 (p = 0.0063) and later TNM stage (p < 0.0001). Patients with high DDX27 expression turned out a worse prognosis on overall survival (OS, p = 0.0087) and disease-free survival (DFS, p = 0.0235). Overexpression of DDX27 could enhance the expression of biomarkers related to stemness and promote stem cell-like activities such as proliferation and migration in breast cancer cells.

Conclusion

DDX27 can enhance stem cell-like properties and cause poor prognosis in breast cancer, also may be expected to become a potential biomarker for breast cancer therapy.
Appendix
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Literature
2.
go back to reference Rocak S, Linder P. DEAD-box proteins: the driving forces behind RNA metabolism. Nat Rev Mol Cell Biol. 2004;5(3):232–41.CrossRef Rocak S, Linder P. DEAD-box proteins: the driving forces behind RNA metabolism. Nat Rev Mol Cell Biol. 2004;5(3):232–41.CrossRef
3.
go back to reference Linder P, Jankowsky E. From unwinding to clamping—the DEAD box RNA helicase family. Nat Rev Mol Cell Biol. 2011;12(8):505–16.CrossRef Linder P, Jankowsky E. From unwinding to clamping—the DEAD box RNA helicase family. Nat Rev Mol Cell Biol. 2011;12(8):505–16.CrossRef
4.
go back to reference Song H, Ji X. The mechanism of RNA duplex recognition and unwinding by DEAD-box helicase DDX3X. Nat Commun. 2019;10(1):3085.CrossRef Song H, Ji X. The mechanism of RNA duplex recognition and unwinding by DEAD-box helicase DDX3X. Nat Commun. 2019;10(1):3085.CrossRef
5.
go back to reference Hondele M, Sachdev R, Heinrich S, Wang J, Vallotton P, Fontoura BMA, et al. DEAD-box ATPases are global regulators of phase-separated organelles. Nature. 2019;573(7772):144–8.CrossRef Hondele M, Sachdev R, Heinrich S, Wang J, Vallotton P, Fontoura BMA, et al. DEAD-box ATPases are global regulators of phase-separated organelles. Nature. 2019;573(7772):144–8.CrossRef
6.
go back to reference Tsai TY, Wang WT, Li HK, Chen WJ, Tsai YH, Chao CH, et al. RNA helicase DDX3 maintains lipid homeostasis through upregulation of the microsomal triglyceride transfer protein by interacting with HNF4 and SHP. Sci Rep. 2017;7: 41452.CrossRef Tsai TY, Wang WT, Li HK, Chen WJ, Tsai YH, Chao CH, et al. RNA helicase DDX3 maintains lipid homeostasis through upregulation of the microsomal triglyceride transfer protein by interacting with HNF4 and SHP. Sci Rep. 2017;7: 41452.CrossRef
7.
go back to reference Li Z, Zhou M, Cai Z, Liu H, Zhong W, Hao Q, et al. RNA-binding protein DDX1 is responsible for fatty acid-mediated repression of insulin translation. Nucleic Acids Res. 2018;46(22):12052–66.CrossRef Li Z, Zhou M, Cai Z, Liu H, Zhong W, Hao Q, et al. RNA-binding protein DDX1 is responsible for fatty acid-mediated repression of insulin translation. Nucleic Acids Res. 2018;46(22):12052–66.CrossRef
8.
go back to reference Sarkar M, Ghosh MK. DEAD box RNA helicases: crucial regulators of gene expression and oncogenesis. Front Biosci. 2016;21:225–50.CrossRef Sarkar M, Ghosh MK. DEAD box RNA helicases: crucial regulators of gene expression and oncogenesis. Front Biosci. 2016;21:225–50.CrossRef
9.
go back to reference Kellner M, Rohrmoser M, Forne I, Voss K, Burger K, Muhl B, et al. DEAD-box helicase DDX27 regulates 3′ end formation of ribosomal 47S RNA and stably associates with the PeBoW-complex. Exp Cell Res. 2015;334(1):146–59.CrossRef Kellner M, Rohrmoser M, Forne I, Voss K, Burger K, Muhl B, et al. DEAD-box helicase DDX27 regulates 3′ end formation of ribosomal 47S RNA and stably associates with the PeBoW-complex. Exp Cell Res. 2015;334(1):146–59.CrossRef
10.
go back to reference Bennett AH, O’Donohue MF, Gundry SR, Chan AT, Widrick J, Draper I, et al. RNA helicase, DDX27 regulates skeletal muscle growth and regeneration by modulation of translational processes. PLoS Genet. 2018;14(3): e1007226.CrossRef Bennett AH, O’Donohue MF, Gundry SR, Chan AT, Widrick J, Draper I, et al. RNA helicase, DDX27 regulates skeletal muscle growth and regeneration by modulation of translational processes. PLoS Genet. 2018;14(3): e1007226.CrossRef
11.
go back to reference Tsukamoto Y, Fumoto S, Noguchi T, Yanagihara K, Hirashita Y, Nakada C, et al. Expression of DDX27 contributes to colony-forming ability of gastric cancer cells and correlates with poor prognosis in gastric cancer. Am J Cancer Res. 2015;5(10):2998–3014.PubMedPubMedCentral Tsukamoto Y, Fumoto S, Noguchi T, Yanagihara K, Hirashita Y, Nakada C, et al. Expression of DDX27 contributes to colony-forming ability of gastric cancer cells and correlates with poor prognosis in gastric cancer. Am J Cancer Res. 2015;5(10):2998–3014.PubMedPubMedCentral
12.
go back to reference Tang J, Chen H, Wong CC, Liu D, Li T, Wang X, et al. DEAD-box helicase 27 promotes colorectal cancer growth and metastasis and predicts poor survival in CRC patients. Oncogene. 2018;37(22):3006–21.CrossRef Tang J, Chen H, Wong CC, Liu D, Li T, Wang X, et al. DEAD-box helicase 27 promotes colorectal cancer growth and metastasis and predicts poor survival in CRC patients. Oncogene. 2018;37(22):3006–21.CrossRef
13.
go back to reference Wang D, Zhu ZZ, Jiang H, Zhu J, Cong WM, Wen BJ, et al. Multiple genes identified as targets for 20q13.12–13.33 gain contributing to unfavorable clinical outcomes in patients with hepatocellular carcinoma. Hepatol Int. 2015;9(3):438–46.CrossRef Wang D, Zhu ZZ, Jiang H, Zhu J, Cong WM, Wen BJ, et al. Multiple genes identified as targets for 20q13.12–13.33 gain contributing to unfavorable clinical outcomes in patients with hepatocellular carcinoma. Hepatol Int. 2015;9(3):438–46.CrossRef
14.
go back to reference Miyoshi N, Mizushima T, Doki Y, Mori M. Cancer stem cells in relation to treatment. Jpn J Clin Oncol. 2019;49(3):232–7.CrossRef Miyoshi N, Mizushima T, Doki Y, Mori M. Cancer stem cells in relation to treatment. Jpn J Clin Oncol. 2019;49(3):232–7.CrossRef
15.
go back to reference Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, et al. Cancer stem cells—perspectives on current status and future directions: AACR workshop on cancer stem cells. Cancer Res. 2006;66(19):9339–44.CrossRef Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, et al. Cancer stem cells—perspectives on current status and future directions: AACR workshop on cancer stem cells. Cancer Res. 2006;66(19):9339–44.CrossRef
16.
go back to reference Pece S, Tosoni D, Confalonieri S, Mazzarol G, Vecchi M, Ronzoni S, et al. Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell. 2010;140(1):62–73.CrossRef Pece S, Tosoni D, Confalonieri S, Mazzarol G, Vecchi M, Ronzoni S, et al. Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell. 2010;140(1):62–73.CrossRef
18.
go back to reference Zhou F, Liu Y, Rohde C, Pauli C, Gerloff D, Kohn M, et al. AML1-ETO requires enhanced C/D box snoRNA/RNP formation to induce self-renewal and leukaemia. Nat Cell Biol. 2017;19(7):844–55.CrossRef Zhou F, Liu Y, Rohde C, Pauli C, Gerloff D, Kohn M, et al. AML1-ETO requires enhanced C/D box snoRNA/RNP formation to induce self-renewal and leukaemia. Nat Cell Biol. 2017;19(7):844–55.CrossRef
19.
go back to reference Santoriello C, Sporrij A, Yang S, Flynn RA, Henriques T, Dorjsuren B, et al. RNA helicase DDX21 mediates nucleotide stress responses in neural crest and melanoma cells. Nat Cell Biol. 2020;22(4):372–9.CrossRef Santoriello C, Sporrij A, Yang S, Flynn RA, Henriques T, Dorjsuren B, et al. RNA helicase DDX21 mediates nucleotide stress responses in neural crest and melanoma cells. Nat Cell Biol. 2020;22(4):372–9.CrossRef
20.
go back to reference Alqahtani H, Gopal K, Gupta N, Jung K, Alshareef A, Ye X, et al. DDX17 (P72), a Sox2 binding partner, promotes stem-like features conferred by Sox2 in a small cell population in estrogen receptor-positive breast cancer. Cell Signal. 2016;28(2):42–50.CrossRef Alqahtani H, Gopal K, Gupta N, Jung K, Alshareef A, Ye X, et al. DDX17 (P72), a Sox2 binding partner, promotes stem-like features conferred by Sox2 in a small cell population in estrogen receptor-positive breast cancer. Cell Signal. 2016;28(2):42–50.CrossRef
21.
go back to reference Kao SH, Cheng WC, Wang YT, Wu HT, Yeh HY, Chen YJ, et al. Regulation of miRNA biogenesis and histone modification by K63-polyubiquitinated DDX17 controls cancer stem-like features. Cancer Res. 2019;79(10):2549–63.PubMed Kao SH, Cheng WC, Wang YT, Wu HT, Yeh HY, Chen YJ, et al. Regulation of miRNA biogenesis and histone modification by K63-polyubiquitinated DDX17 controls cancer stem-like features. Cancer Res. 2019;79(10):2549–63.PubMed
22.
go back to reference Yang C, Li D, Bai Y, Song S, Yan P, Wu R, et al. DEAD-box helicase 27 plays a tumor-promoter role by regulating the stem cell-like activity of human colorectal cancer cells. Onco Targets Ther. 2019;12:233–41.CrossRef Yang C, Li D, Bai Y, Song S, Yan P, Wu R, et al. DEAD-box helicase 27 plays a tumor-promoter role by regulating the stem cell-like activity of human colorectal cancer cells. Onco Targets Ther. 2019;12:233–41.CrossRef
23.
go back to reference Lanczky A, Nagy A, Bottai G, Munkacsy G, Szabo A, Santarpia L, et al. miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients. Breast Cancer Res Treat. 2016;160(3):439–46.CrossRef Lanczky A, Nagy A, Bottai G, Munkacsy G, Szabo A, Santarpia L, et al. miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients. Breast Cancer Res Treat. 2016;160(3):439–46.CrossRef
24.
go back to reference Yan Y, Liu F, Han L, Zhao L, Chen J, Olopade OI, et al. HIF-2alpha promotes conversion to a stem cell phenotype and induces chemoresistance in breast cancer cells by activating Wnt and Notch pathways. J Exp Clin Cancer Res. 2018;37(1):256.CrossRef Yan Y, Liu F, Han L, Zhao L, Chen J, Olopade OI, et al. HIF-2alpha promotes conversion to a stem cell phenotype and induces chemoresistance in breast cancer cells by activating Wnt and Notch pathways. J Exp Clin Cancer Res. 2018;37(1):256.CrossRef
25.
go back to reference Zheng A, Song X, Zhang L, Zhao L, Mao X, Wei M, et al. Long non-coding RNA LUCAT1/miR-5582-3p/TCF7L2 axis regulates breast cancer stemness via Wnt/beta-catenin pathway. J Exp Clin Cancer Res. 2019;38(1):305.CrossRef Zheng A, Song X, Zhang L, Zhao L, Mao X, Wei M, et al. Long non-coding RNA LUCAT1/miR-5582-3p/TCF7L2 axis regulates breast cancer stemness via Wnt/beta-catenin pathway. J Exp Clin Cancer Res. 2019;38(1):305.CrossRef
26.
go back to reference Hayden MS, Ghosh S. Shared principles in NF-kappaB signaling. Cell. 2008;132(3):344–62.CrossRef Hayden MS, Ghosh S. Shared principles in NF-kappaB signaling. Cell. 2008;132(3):344–62.CrossRef
27.
go back to reference Shostak K, Chariot A. NF-kappaB, stem cells and breast cancer: the links get stronger. Breast Cancer Res. 2011;13(4):214.CrossRef Shostak K, Chariot A. NF-kappaB, stem cells and breast cancer: the links get stronger. Breast Cancer Res. 2011;13(4):214.CrossRef
28.
go back to reference Huber MA, Azoitei N, Baumann B, Grunert S, Sommer A, Pehamberger H, et al. NF-kappaB is essential for epithelial–mesenchymal transition and metastasis in a model of breast cancer progression. J Clin Invest. 2004;114(4):569–81.CrossRef Huber MA, Azoitei N, Baumann B, Grunert S, Sommer A, Pehamberger H, et al. NF-kappaB is essential for epithelial–mesenchymal transition and metastasis in a model of breast cancer progression. J Clin Invest. 2004;114(4):569–81.CrossRef
29.
go back to reference Yoshida GJ. Emerging roles of Myc in stem cell biology and novel tumor therapies. J Exp Clin Cancer Res. 2018;37(1):173.CrossRef Yoshida GJ. Emerging roles of Myc in stem cell biology and novel tumor therapies. J Exp Clin Cancer Res. 2018;37(1):173.CrossRef
Metadata
Title
DEAD-box helicase 27 enhances stem cell-like properties with poor prognosis in breast cancer
Authors
Shan Li
Jinfei Ma
Ang Zheng
Xinyue Song
Si Chen
Feng Jin
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2021
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-021-03011-0

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