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. 2020 Jul;36(7):501-507.
doi: 10.1002/kjm2.12204. Epub 2020 Mar 20.

Inhibiting ubiquitin conjugating enzyme E2 N by microRNA-590-3p reduced cell growth of cervical carcinoma

Ting-Ting Song  1 , Fei Xu  1 , Wei Wang  1
Affiliations

Inhibiting ubiquitin conjugating enzyme E2 N by microRNA-590-3p reduced cell growth of cervical carcinoma

Ting-Ting Song et al. Kaohsiung J Med Sci. 2020 Jul.

Abstract

The ubiquitin conjugating enzyme E2 N (UBE2N) has been reported to be involved in the tumorigenesis of several tumors, but its function in cervical carcinoma has not been investigated yet. In the present study, UBE2N was found elevated in cervical carcinoma, and patients with high UBE2N had a shorter overall survival than patients with low expression. Additionally, knockdown of UBE2N decreased the activation of MEK1/2 and p38 in cervical carcinoma cells, and UBE2N knockdown also markedly inhibited cervical carcinoma cell growth. Our further studies found that microRNA-590-3p (miR-590-3p) was significantly decreased in cervical carcinoma, and patients with high miR-590-3p had a longer overall survival than patients with low expression. Moreover, miR-590-3p expression was found negatively correlated with UBE2N expression in cervical carcinoma, and our further studies showed that miR-590-3p targeted UBE2N and inhibited its expression in cervical carcinoma. Overexpression of miR-590-3p could inhibit cervical carcinoma cell growth, but enhanced UBE2N could rescue miR-590-3p-induced cell growth inhibition in cervical carcinoma. This study indicated that targeting miR-590-3p/UBE2N axis could be a potential strategy for the treatment of cervical carcinoma.

Keywords: UBE2N; cell growth; cervical carcinoma; microRNA-590-3p; target.

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Conflict of interest statement

The authors declare no potential conflict of interest.

Figures

Figure 1
Figure 1
UBE2N is elevated in cervical carcinoma, and predicts a poor prognosis for patients. A, GEPIA matched with TCGA and GTEx (http://gepia2.cancer‐pku.cn) was used to analyze UBE2N expression. B, Kaplan‐Meier plotter (http://kmplot.com) was used to analyze the overall survival in cervical squamous cell carcinoma. C, Sixteen pairs of paracancerous tissues and tumor tissues of cervical cancer were used for qRT‐PCR. D, Statistical analysis for Figure 1C. *P < .05, **P < .01. CESC, Cervical squamous cell carcinoma and endocervical adenocarcinoma; qRT‐PCR, quantitative real‐time polymerase chain reaction
Figure 2
Figure 2
Knockdown of UBE2N inhibits cell growth of cervical carcinoma by suppressing MAPK activation. A, Cells were infected with indicated lentivirus for 3 days, and then infected cells were prepared for qRT‐PCR analysis. B, HeLa and, C, SiHa cells infected with indicated lentivirus were cultured for indicated times, followed by CCK‐8 assay. D, Cells were infected with indicated lentivirus for 48 hours, and then cells were used for western blot. *P < .05, **P < .01; # P < .05, ## P < .01. qRT‐PCR, quantitative real‐time polymerase chain reaction
Figure 3
Figure 3
MiR‐590‐3p is downregulated in cervical carcinoma, and negatively correlated with UBE2N. A, Sixteen pairs of paracancerous tissues and tumor tissues of cervical cancer were used for qRT‐PCR to detect miR‐590‐3p expression. B, Statistical analysis for Figure 3B. C, Kaplan‐Meier plotter was used to analyze the overall survival in cervical squamous cell carcinoma. D, Correlation analysis for miR‐590‐3p and UBE2N expression in 16 cervical carcinoma tumor tissues. **P < .01. qRT‐PCR, quantitative real‐time polymerase chain reaction
Figure 4
Figure 4
MiR‐590‐3p targets UBE2N and inhibits its expression in cervical carcinoma. A, the binding sites of miR‐590‐3p in UBE2N 3'UTR were predicted online (http://www.microrna.org). MiR‐NC or miR‐590‐3p mimics were transfected into HeLa and SiHa cells for 3 days, and then cells were used for, B, qRT‐PCR analysis or, C, western blot. D, HeLa cells were transfected with indicated miRNAs or plasmids. Three days later, cells were lysed for luciferase assay. **P < .01, ## P < .01. N.s. means nonsense. qRT‐PCR, quantitative real‐time polymerase chain reaction; Mut, mutated; WT, wild‐type
Figure 5
Figure 5
Overexpression of UBE2N rescued miR‐590‐3p‐induced cell growth inhibition in cervical carcinoma, A,. HeLa and SiHa cells were transfected with miR‐NC or miR‐590‐3p mimics for 3 days, followed by qRT‐PCR. B, HeLa and, C, SiHa cells were transfected with miR‐NC or miR‐590‐3p mimics for indicated times, followed by CCK‐8. D, HeLa cells were transfected with miR‐NC, miR‐590‐3p mimics, or Myc‐UBE2N plasmids for 3 days, followed by CCK‐8. *P < .05, **P < .01, ## P < .01. qRT‐PCR, quantitative real‐time polymerase chain reaction
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