Comprehensive analysis of UBE2C expression and its potential roles and mechanisms in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) ranks one of the most common and lethal cancers all over the world. Previous studies suggest that ubiquitin-conjugating enzyme E2C (UBE2C) serves as an oncogene in human cancers. However, its expression, diagnosis, prognosis and potential mechanisms in HCC remain largely unknown. In this study, the expression of UBE2C in HCC was first analyzed by comprehensive bioinformatic analysis. ROC curve analysis and survival analysis were employed to assess the diagnostic and prognostic roles of UBE2C in HCC. UBE2C promoter methylation level and upstream regulatory miRNAs of UBE2C in HCC were explored. The present work demonstrated that UBE2C was significantly upregulated in HCC compared with normal controls. We also found significant diagnostic and prognostic values of UBE2C in HCC. Promoter methylation of UBE2C was obviously decreased in HCC and was negatively correlated with UBE2C mRNA expression. 10 miRNAs were predicted to potentially bind to UBE2C. In vitro assay and bioinformatic correlation analysis together revealed that hsa-miR-193b-3p might be another key upstream regulatory mechanism of UBE2C in HCC. In conclusion, UBE2C is overexpressed in HCC and may serve as a key diagnostic/prognostic biomarker for patients with HCC.

Keywords: UBE2C; diagnosis; hepatocellular carcinoma; liver cancer; microRNA (miRNA); prognosis.

Figure 1

The expression level of UBE2C in HCC. (A) The details of the meta-analyses of UBE2C in HCC from Oncomine database. The legends below the meta-analytical result present detailed information of the 4 selected datasets. UBE2C expression in patients with HCC based on the Chen Liver dataset (B), Roessler Liver dataset (C), Roessler Liver 2 dataset (D) and Wurmbach Liver dataset (E) from Oncomine database. (F) UBE2C expression in 369 HCC samples (TCGA) compared with 50 normal controls (TCGA) from GEPIA database. (G) UBE2C expression in 369 HCC samples (TCGA) compared with 160 normal controls (TCGA and GTEx) from GEPIA database. (H) Expression difference of UBE2C among various major stage of HCC from GEPIA database. “^*” represents P-value < 0.05.

Figure 2

The diagnostic value of UBE2C in HCC.

Figure 3

The prognostic value of UBE2C in HCC. HCC patients with higher expression of UBE2C indicated a poorer OS (A), RFS (B), PFS (C) and DSS (D). Logrank P-value < 0.05 was considered as statistically significant. Abbreviations: OS: overall survival; RFS: relapse free survival; PFS: progression free survival; DSS: disease specific survival.

Figure 4

Survival analysis for UBE2C in HCC and adjacent normal samples. The prognostic values of UBE2C in HCC and adjacent normal liver tissues in HCCDB6 (A), HCCDB15 (B) and HCCDB18 (C) datasets determined by HCCDB database.

Figure 5

Promoter methylation level of UBE2C in HCC. (A) UBE2C promoter methylation level was significantly decreased in HCC compared with normal controls determined by UALCAN database. (B) UBE2C promoter methylation level was negatively linked to UBE2C mRNA expression determined by cBioPortal database. “^*” represents P-value < 0.05.

Figure 6

A potential miRNA-UBE2C regulatory network established by Cytoscape software (Version 3.6.0).

Figure 7

Identification of hsa-miR-193b-3p as a key regulator of UBE2C in HCC. Expression change of UBE2C after overexpression of 10 potential upstream miRNAs in HepG2 (A) and Huh7 (B) cell lines. (C) Expression change of UBE2C after silence of 10 potential upstream miRNAs in HepG2 and Huh7 cell lines. (D) Hsa-miR-193b-3p expression was significantly negatively correlated with UBE2C expression in HCC determined by starBase database. “^*” represents P-value < 0.05.

Figure 8

The dysregulated mechanism graph of UBE2C in HCC.