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MiR-525-5p Repressed Metastasis and Anoikis Resistance in Cervical Cancer via Blocking UBE2C/ZEB1/2 Signal Axis

  • Mei Chen
  • Li-xiu LiuEmail author
Original Article
  • 49 Downloads

Abstract

Background

Accumulating evidence indicated that miRNAs are important regulators involved in cancer biology.

Aims

We aimed to investigate the biological functions and potentially underlying molecular mechanism of miR-525-5p in CC.

Methods

RT-PCR and Western blot assay were performed to detect mRNA and protein expression. Cell proliferation, anoikis resistance, and cell invasion were analyzed.

Results

We observed that the expression of miR-525-5p was declined in several CC cell lines. Additionally, introduction of miR-525-5p dramatically hampered cell viability, invasiveness, and migration ability through modulating epithelial-to-mesenchymal transition (EMT) marked genes as reflected by the upregulation of E-cadherin, as well as the downregulation of vimentin and N-cadherin. Furthermore, administration of miR-525-5p markedly reduced anchorage-independent growth and anoikis resistance accompanied by a decrease in the expression of anti-apoptotic protein Bcl-2 and an increase in the expression of pro-apoptotic protein Bax, C-caspase 3, and C-PARP1. Most importantly, analysis using publicly available algorithms predicted that UBE2C was a direct and functional target of miR-525-5p. Luciferase assays coupled with RT-PCR and Western blot analysis further verified that miR-525-5p negatively regulated UBE2C expression. Interestingly, miR-525-5p modulated ZEB1/2 expression via targeting UBE2C. Mechanically, administration of UBE2C partially blunted the salutary effects of miR-525-5p on invasive ability, EMT, and anoikis resistance, indicating that miR-525-5p acts as a tumor suppressor in CC largely through repression of UBE2C/ZEB1/2 signaling.

Conclusions

Taken together, our data identify a novel signaling axis of miR-525-5p/UBE2C/ZEB1/2 in repressing EMT and anoikis resistance, and likely serve as a potential therapeutic target for CC metastasis and prognosis as well as a therapeutic application.

Keywords

MiR-525-5p Metastasis Anoikis resistance UBE2C/ZEB1/2 signal axis Cervical cancer 

Notes

Acknowledgments

The work was supported by the Science and Technology Project of Xianyang (2017k02-75).

Compliance with Ethical Standards

Conflict of interest

The authors declare that there is no conflict of interest for this work.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of GynecologyAffiliated Hospital of Shaanxi University of Chinese MedicineXianyangPeople’s Republic of China

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