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

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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.

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Acknowledgments

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

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Authors and Affiliations

  1. Department of Gynecology, Affiliated Hospital of Shaanxi University of Chinese Medicine, No. 2, Weiyang West Road, Xianyang, 712021, Shaanxi, People’s Republic of China

    Mei Chen & Li-xiu Liu

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  1. Mei Chen
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Correspondence to Li-xiu Liu.

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Chen, M., Liu, Lx. MiR-525-5p Repressed Metastasis and Anoikis Resistance in Cervical Cancer via Blocking UBE2C/ZEB1/2 Signal Axis. Dig Dis Sci 65, 2442–2451 (2020). https://doi.org/10.1007/s10620-019-05916-9

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