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Published in: Diagnostic Pathology 1/2020

Open Access 01-12-2020 | Breast Cancer | Research

Circular RNA KIF4A promotes cell migration, invasion and inhibits apoptosis through miR-152/ZEB1 axis in breast cancer

Authors: Yongping Jin, Liu Yang, Xia Li, Fangli Liu

Published in: Diagnostic Pathology | Issue 1/2020

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Abstract

Background

Circular RNAs (circRNAs) have been demonstrated to exert crucial mediators in tumor initiation and development. Nevertheless, the roles of circKIF4A in breast cancer (BC) are still not very clear.

Methods

Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine the expression of circKIF4A, miR-152, zinc finger E-box binding homeobox 1 (ZEB1) mRNA and caspase-3. Western blot assay was utilized to examine the protein level of ZEB1. Transwell assay and flow-cytometric analysis were adopted for the evaluation of cell migration, invasion and apoptosis, respectively. The associations among circKIF4A, miR-152 and ZEB1 were predicted by online websites and verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay.

Results

CircKIF4A and ZEB1 were conspicuously upregulated and miR-152 was markedly reduced in BC tissues and cells. Deficiency of circKIF4A repressed migration, invasion and induced apoptosis of BC cells. Moreover, circKIF4A was confirmed to be a sponge of miR-152 and miR-152 could bind to ZEB1. MiR-152 inhibition or ZEB1 overexpression abolished the impacts of circKIF4A knockdown on cell migration, invasion and apoptosis in BC.

Conclusion

Silencing of circKIF4A hampered cell metastasis and promoted apoptosis by regulating ZEB1 via sponging miR-152 in BC.
Literature
1.
go back to reference Bray F, Soerjomataram I. The changing global burden of cancer: transitions in human development and implications for cancer prevention and control. Cancer. 2015;3:23–44. Bray F, Soerjomataram I. The changing global burden of cancer: transitions in human development and implications for cancer prevention and control. Cancer. 2015;3:23–44.
2.
go back to reference Newman LA. Disparities in breast cancer and african ancestry: a global perspective. Breast J. 2015;21(2):133–9.PubMed Newman LA. Disparities in breast cancer and african ancestry: a global perspective. Breast J. 2015;21(2):133–9.PubMed
3.
go back to reference Xue J, Chi Y, Chen Y, Huang S, Ye X, Niu J, Wang W, Pfeffer LM, Shao Z, Wu ZH. MiRNA-621 sensitizes breast cancer to chemotherapy by suppressing FBXO11 and enhancing p53 activity. Oncogene. 2016;35(4):448–58.PubMed Xue J, Chi Y, Chen Y, Huang S, Ye X, Niu J, Wang W, Pfeffer LM, Shao Z, Wu ZH. MiRNA-621 sensitizes breast cancer to chemotherapy by suppressing FBXO11 and enhancing p53 activity. Oncogene. 2016;35(4):448–58.PubMed
4.
go back to reference Cedolini C, Bertozzi S, Londero AP, Bernardi S, Seriau L, Concina S, Cattin F, Risaliti A. Type of breast cancer diagnosis, screening, and survival. Clin Breast Cancer. 2014;14(4):235–40.PubMed Cedolini C, Bertozzi S, Londero AP, Bernardi S, Seriau L, Concina S, Cattin F, Risaliti A. Type of breast cancer diagnosis, screening, and survival. Clin Breast Cancer. 2014;14(4):235–40.PubMed
6.
go back to reference Mercer TR, Mattick JS. Structure and function of long noncoding RNAs in epigenetic regulation. Nat Struct Mol Biol. 2013;20(3):300–7.PubMed Mercer TR, Mattick JS. Structure and function of long noncoding RNAs in epigenetic regulation. Nat Struct Mol Biol. 2013;20(3):300–7.PubMed
7.
go back to reference Kulcheski FR, Christoff AP, Margis R. Circular RNAs are miRNA sponges and can be used as a new class of biomarker. J Biotechnol. 2016;238:42–51.PubMed Kulcheski FR, Christoff AP, Margis R. Circular RNAs are miRNA sponges and can be used as a new class of biomarker. J Biotechnol. 2016;238:42–51.PubMed
8.
go back to reference Yu J, Xu QG, Wang ZG, Yang Y, Zhang L, Ma JZ, Sun SH, Yang F, Zhou WP. Circular RNA cSMARCA5 inhibits growth and metastasis in hepatocellular carcinoma. J Hepatol. 2018;68(6):1214–27.PubMed Yu J, Xu QG, Wang ZG, Yang Y, Zhang L, Ma JZ, Sun SH, Yang F, Zhou WP. Circular RNA cSMARCA5 inhibits growth and metastasis in hepatocellular carcinoma. J Hepatol. 2018;68(6):1214–27.PubMed
9.
go back to reference Zhang J, Liu H, Hou L, Wang G, Zhang R, Huang Y, Chen X, Zhu J. Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression. Mol Cancer. 2017;16(1):151.PubMedPubMedCentral Zhang J, Liu H, Hou L, Wang G, Zhang R, Huang Y, Chen X, Zhu J. Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression. Mol Cancer. 2017;16(1):151.PubMedPubMedCentral
10.
go back to reference Han D, Li J, Wang H, Su X, Hou J, Gu Y, Qian C, Lin Y, Liu X, Huang M. Circular RNA circMTO1 acts as the sponge of microRNA-9 to suppress hepatocellular carcinoma progression. Hepatology. 2017;66(4):1151–64.PubMed Han D, Li J, Wang H, Su X, Hou J, Gu Y, Qian C, Lin Y, Liu X, Huang M. Circular RNA circMTO1 acts as the sponge of microRNA-9 to suppress hepatocellular carcinoma progression. Hepatology. 2017;66(4):1151–64.PubMed
11.
go back to reference Tang H, Huang X, Wang J, Yang L, Kong Y, Gao G, Zhang L, Chen ZS, Xie X. circKIF4A acts as a prognostic factor and mediator to regulate the progression of triple-negative breast cancer. Mol Cancer. 2019;18(1):23.PubMedPubMedCentral Tang H, Huang X, Wang J, Yang L, Kong Y, Gao G, Zhang L, Chen ZS, Xie X. circKIF4A acts as a prognostic factor and mediator to regulate the progression of triple-negative breast cancer. Mol Cancer. 2019;18(1):23.PubMedPubMedCentral
12.
go back to reference Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495(7441):384–8.PubMed Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495(7441):384–8.PubMed
13.
go back to reference Ambros V. microRNAs: tiny regulators with great potential. Cell. 2001;107(7):823–6.PubMed Ambros V. microRNAs: tiny regulators with great potential. Cell. 2001;107(7):823–6.PubMed
14.
go back to reference Hua Y, Duan S, Murmann AE, Larsen N, Kjems J, Lund AH, Peter ME. miRConnect: identifying effector genes of miRNAs and miRNA families in cancer cells. PloS one. 2011;6(10):e26521.PubMedPubMedCentral Hua Y, Duan S, Murmann AE, Larsen N, Kjems J, Lund AH, Peter ME. miRConnect: identifying effector genes of miRNAs and miRNA families in cancer cells. PloS one. 2011;6(10):e26521.PubMedPubMedCentral
15.
16.
go back to reference Maimaitiming A, Wusiman A, Aimudula A, Kuerban X, Su P. microRNA-152 inhibits cell proliferation, migration and invasion in breast cancer. Oncol Res. 2020;28(1):13–9.PubMed Maimaitiming A, Wusiman A, Aimudula A, Kuerban X, Su P. microRNA-152 inhibits cell proliferation, migration and invasion in breast cancer. Oncol Res. 2020;28(1):13–9.PubMed
17.
go back to reference Bakiri L, Macho-Maschler S, Custic I, Niemiec J, Guio-Carrion A, Hasenfuss S, Eger A, Müller M, Beug H, Wagner E. Fra-1/AP-1 induces EMT in mammary epithelial cells by modulating Zeb1/2 and TGFβ expression. Cell Death Differ. 2015;22(2):336–50.PubMed Bakiri L, Macho-Maschler S, Custic I, Niemiec J, Guio-Carrion A, Hasenfuss S, Eger A, Müller M, Beug H, Wagner E. Fra-1/AP-1 induces EMT in mammary epithelial cells by modulating Zeb1/2 and TGFβ expression. Cell Death Differ. 2015;22(2):336–50.PubMed
18.
go back to reference Schmalhofer O, Brabletz S, Brabletz T. E-cadherin, β-catenin, and ZEB1 in malignant progression of cancer. Cancer Metastasis Rev. 2009;28(1–2):151–66.PubMed Schmalhofer O, Brabletz S, Brabletz T. E-cadherin, β-catenin, and ZEB1 in malignant progression of cancer. Cancer Metastasis Rev. 2009;28(1–2):151–66.PubMed
19.
go back to reference Sekido R, Takagi T, Okanami M, Moribe H, Yamamura M, Higashi Y, Kondoh H. Organization of the gene encoding transcriptional repressor δEF1 and cross-species conservation of its domains. Gene. 1996;173(2):227–32.PubMed Sekido R, Takagi T, Okanami M, Moribe H, Yamamura M, Higashi Y, Kondoh H. Organization of the gene encoding transcriptional repressor δEF1 and cross-species conservation of its domains. Gene. 1996;173(2):227–32.PubMed
20.
go back to reference Gong J, Wang Y, Jiang B, Xu B, Hu C. Impact of high-mobility-group A2 overexpression on epithelial-mesenchymal transition in pancreatic cancer. Cancer Manag Res. 2019;11:4075–84.PubMedPubMedCentral Gong J, Wang Y, Jiang B, Xu B, Hu C. Impact of high-mobility-group A2 overexpression on epithelial-mesenchymal transition in pancreatic cancer. Cancer Manag Res. 2019;11:4075–84.PubMedPubMedCentral
21.
go back to reference Fan MJ, Zou YH, He PJ, Zhang S, Sun XM, Li CZ. Long non-coding RNA promotes epithelial-mesenchymal transition of cervical cancer by regulating the miR-101-3p/ZEB1 axis. Biosci Rep. 2019;39(6):BSR20181339. Fan MJ, Zou YH, He PJ, Zhang S, Sun XM, Li CZ. Long non-coding RNA promotes epithelial-mesenchymal transition of cervical cancer by regulating the miR-101-3p/ZEB1 axis. Biosci Rep. 2019;39(6):BSR20181339.
22.
go back to reference Chen Y, Sumardika IW, Tomonobu N, Kinoshita R, Inoue Y, Iioka H, Mitsui Y, Saito K, Ruma IMW, Sato H, Yamauchi A, Murata H, Yamamoto KI3, Tomida S, Shien K, Yamamoto H, Soh J, Futami J, Kubo M, Putranto EW, Murakami T, Liu M, Hibino T, Nishibori M, Kondo E, Toyooka S, Sakaguchi M. Critical role of the MCAM-ETV4 axis triggered by extracellular S100A8/A9 in breast cancer aggressiveness. Neoplasia (New York, NY). 2019;21(7):627–40. Chen Y, Sumardika IW, Tomonobu N, Kinoshita R, Inoue Y, Iioka H, Mitsui Y, Saito K, Ruma IMW, Sato H, Yamauchi A, Murata H, Yamamoto KI3, Tomida S, Shien K, Yamamoto H, Soh J, Futami J, Kubo M, Putranto EW, Murakami T, Liu M, Hibino T, Nishibori M, Kondo E, Toyooka S, Sakaguchi M. Critical role of the MCAM-ETV4 axis triggered by extracellular S100A8/A9 in breast cancer aggressiveness. Neoplasia (New York, NY). 2019;21(7):627–40.
23.
go back to reference Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C T method. Nat Protocol. 2008;3(6):1101–8. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C T method. Nat Protocol. 2008;3(6):1101–8.
25.
go back to reference Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–E86. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–E86.
26.
go back to reference Jiang LH, Hou JC, Zhong SL, Zhou SY, Zhu LP, Li J, Wang DD, Sun DW, Ji ZL, Tang JH. Circular RNA hsa_circ_0052112 promotes cell migration and invasion by acting as sponge for miR-125a-5p in breast cancer. Biomed Pharmacother. 2018;107:1342–53.PubMed Jiang LH, Hou JC, Zhong SL, Zhou SY, Zhu LP, Li J, Wang DD, Sun DW, Ji ZL, Tang JH. Circular RNA hsa_circ_0052112 promotes cell migration and invasion by acting as sponge for miR-125a-5p in breast cancer. Biomed Pharmacother. 2018;107:1342–53.PubMed
27.
go back to reference Wang S, Li Q, Wang Y, Li X, Wang R, Kang Y, Xue X, Meng R, Wei Q, Feng X. Upregulation of circ-UBAP2 predicts poor prognosis and promotes triple-negative breast cancer progression through the miR-661/MTA1 pathway. Biochem Biophys Res Commun. 2018;505(4):996–1002.PubMed Wang S, Li Q, Wang Y, Li X, Wang R, Kang Y, Xue X, Meng R, Wei Q, Feng X. Upregulation of circ-UBAP2 predicts poor prognosis and promotes triple-negative breast cancer progression through the miR-661/MTA1 pathway. Biochem Biophys Res Commun. 2018;505(4):996–1002.PubMed
28.
go back to reference Porter AG, Jänicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999;6(2):99–104.PubMed Porter AG, Jänicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999;6(2):99–104.PubMed
29.
go back to reference Schickel R, Boyerinas B, Park S, Peter M. MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene. 2008;27(45):5959–74.PubMed Schickel R, Boyerinas B, Park S, Peter M. MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene. 2008;27(45):5959–74.PubMed
30.
go back to reference Chen K, Zhang L. LINC00339 regulates ROCK1 by miR-152 to promote cell proliferation and migration in hepatocellular carcinoma. J Cell Biochem. 2019;120(9):14431–43.PubMed Chen K, Zhang L. LINC00339 regulates ROCK1 by miR-152 to promote cell proliferation and migration in hepatocellular carcinoma. J Cell Biochem. 2019;120(9):14431–43.PubMed
31.
go back to reference Feng F, Liu H, Chen A, Xia Q, Zhao Y, Jin X, Huang J. miR-148-3p and miR-152-3p synergistically regulate prostate cancer progression via repressing KLF4. J Cell Biochem. 2019;120(10):17228–39.PubMed Feng F, Liu H, Chen A, Xia Q, Zhao Y, Jin X, Huang J. miR-148-3p and miR-152-3p synergistically regulate prostate cancer progression via repressing KLF4. J Cell Biochem. 2019;120(10):17228–39.PubMed
32.
go back to reference Ghazanchaei A, Mansoori B, Mohammadi A, Biglari A, Baradaran B. Restoration of miR-152 expression suppresses cell proliferation, survival, and migration through inhibition of AKT-ERK pathway in colorectal cancer. J Cell Physiol. 2018;234(1):769–76.PubMed Ghazanchaei A, Mansoori B, Mohammadi A, Biglari A, Baradaran B. Restoration of miR-152 expression suppresses cell proliferation, survival, and migration through inhibition of AKT-ERK pathway in colorectal cancer. J Cell Physiol. 2018;234(1):769–76.PubMed
33.
go back to reference Zhang H, Lu Y, Wang S, Sheng X, Zhang S. MicroRNA-152 acts as a tumor suppressor microRNA by inhibiting Krüppel-like factor 5 in human cervical cancer. Oncol Res. 2019;27(3):335–40.PubMed Zhang H, Lu Y, Wang S, Sheng X, Zhang S. MicroRNA-152 acts as a tumor suppressor microRNA by inhibiting Krüppel-like factor 5 in human cervical cancer. Oncol Res. 2019;27(3):335–40.PubMed
Metadata
Title
Circular RNA KIF4A promotes cell migration, invasion and inhibits apoptosis through miR-152/ZEB1 axis in breast cancer
Authors
Yongping Jin
Liu Yang
Xia Li
Fangli Liu
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2020
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-020-00963-7

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