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

被引:47
作者
Chen, Mei [1 ]
Liu, Li-xiu [1 ]
机构
[1] Shaanxi Univ Chinese Med, Dept Gynecol, Affiliated Hosp, 2 Weiyang West Rd, Xianyang 712021, Shaanxi, Peoples R China
关键词
MiR-525-5p; Metastasis; Anoikis resistance; UBE2C; ZEB1; 2 signal axis; Cervical cancer; EPITHELIAL-MESENCHYMAL TRANSITION; CELLS; ZEB1; EMT; PROGRESSION;
D O I
10.1007/s10620-019-05916-9
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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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页码:2442 / 2451
页数:10
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