UBE2I promotes metastasis and correlates with poor prognosis in hepatocellular carcinoma
Abstract Background A comprehensive investigation of ubiquitin-conjugating enzyme E2I (UBE2I) in cancer is still insufficiency. In this study, we aimed to analyze its role and mechanism in cancer by combination of bioinformatic analysis and experimental validation. Methods The expression profile of...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-06-01
|
| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12935-020-01311-x |
| _version_ | 1811313955256139776 |
|---|---|
| author | Hao Yang Shan Gao Jing Chen Weiyang Lou |
| author_facet | Hao Yang Shan Gao Jing Chen Weiyang Lou |
| author_sort | Hao Yang |
| collection | DOAJ |
| description | Abstract Background A comprehensive investigation of ubiquitin-conjugating enzyme E2I (UBE2I) in cancer is still insufficiency. In this study, we aimed to analyze its role and mechanism in cancer by combination of bioinformatic analysis and experimental validation. Methods The expression profile of UBE2I in human cancers were obtained using GEPIA. Kaplan–Meier plotter was used to assess the prognostic values of UBE2I in diverse types of cancer. ROC curve analysis was employed to determine the diagnostic role of UBE2I in hepatocellular carcinoma (HCC). The expression differences based on various clinicopathological features was evaluated by UALCAN. Wound healing assay and transwell invasion assay were used to detected the effects of UBE2I on migration and invasion of HCC cells, respectively. The miRNA regulatory mechanism of UBE2I was successively investigated by binding prediction, expression analysis, survival analysis and dual-luciferase reporter assay. The correlation of UBE2I mRNA expression and UBE2I promoter methylation level was assessed using cBioPortal. STRING was finally introduced to perform co-expression analysis and enrichment analysis for UBE2I. Results UBE2I was upregulated in HCC, correlated with cancer progression and poor prognosis of HCC. We also found a significant diagnostic value of UBE2I in HCC. Functional experiments revealed that knockdown of UBE2I significantly inhibited HCC migration and invasion. Further research on mechanism suggested that loss of inhibition of hsa-miR-195-3p and dysregulation of UBE2I promoter methylation might account for UBE2I overexpression in HCC. Analysis of UBE2I-invovled regulatory network identified six key genes (NSMCE2, SAE1, UBA2, RANGAP1, SUMO1 and SUMO2) whose expression linked to poor prognosis in HCC. Conclusions In conclusion, UBE2I may be a promising therapeutic target and biomarker in cancer, especially HCC. |
| first_indexed | 2024-04-13T11:03:30Z |
| format | Article |
| id | doaj.art-94112082322c49b4ba0fe56739ad6ade |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-04-13T11:03:30Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-94112082322c49b4ba0fe56739ad6ade2022-12-22T02:49:21ZengBMCCancer Cell International1475-28672020-06-0120111310.1186/s12935-020-01311-xUBE2I promotes metastasis and correlates with poor prognosis in hepatocellular carcinomaHao Yang0Shan Gao1Jing Chen2Weiyang Lou3Clinical Research Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical HospitalDepartment of Anus & Intestine Surgery, Zhejiang Provincial People’s HospitalDepartment of Oncology, First Affiliated Hospital of Jiaxing UniversityDepartment of Breast Surgery, First Affiliated Hospital, College of Medicine, Zhejiang UniversityAbstract Background A comprehensive investigation of ubiquitin-conjugating enzyme E2I (UBE2I) in cancer is still insufficiency. In this study, we aimed to analyze its role and mechanism in cancer by combination of bioinformatic analysis and experimental validation. Methods The expression profile of UBE2I in human cancers were obtained using GEPIA. Kaplan–Meier plotter was used to assess the prognostic values of UBE2I in diverse types of cancer. ROC curve analysis was employed to determine the diagnostic role of UBE2I in hepatocellular carcinoma (HCC). The expression differences based on various clinicopathological features was evaluated by UALCAN. Wound healing assay and transwell invasion assay were used to detected the effects of UBE2I on migration and invasion of HCC cells, respectively. The miRNA regulatory mechanism of UBE2I was successively investigated by binding prediction, expression analysis, survival analysis and dual-luciferase reporter assay. The correlation of UBE2I mRNA expression and UBE2I promoter methylation level was assessed using cBioPortal. STRING was finally introduced to perform co-expression analysis and enrichment analysis for UBE2I. Results UBE2I was upregulated in HCC, correlated with cancer progression and poor prognosis of HCC. We also found a significant diagnostic value of UBE2I in HCC. Functional experiments revealed that knockdown of UBE2I significantly inhibited HCC migration and invasion. Further research on mechanism suggested that loss of inhibition of hsa-miR-195-3p and dysregulation of UBE2I promoter methylation might account for UBE2I overexpression in HCC. Analysis of UBE2I-invovled regulatory network identified six key genes (NSMCE2, SAE1, UBA2, RANGAP1, SUMO1 and SUMO2) whose expression linked to poor prognosis in HCC. Conclusions In conclusion, UBE2I may be a promising therapeutic target and biomarker in cancer, especially HCC.http://link.springer.com/article/10.1186/s12935-020-01311-xUBE2IHepatocellular carcinomaDiagnosisPrognosisMigrationInvasion |
| spellingShingle | Hao Yang Shan Gao Jing Chen Weiyang Lou UBE2I promotes metastasis and correlates with poor prognosis in hepatocellular carcinoma Cancer Cell International UBE2I Hepatocellular carcinoma Diagnosis Prognosis Migration Invasion |
| title | UBE2I promotes metastasis and correlates with poor prognosis in hepatocellular carcinoma |
| title_full | UBE2I promotes metastasis and correlates with poor prognosis in hepatocellular carcinoma |
| title_fullStr | UBE2I promotes metastasis and correlates with poor prognosis in hepatocellular carcinoma |
| title_full_unstemmed | UBE2I promotes metastasis and correlates with poor prognosis in hepatocellular carcinoma |
| title_short | UBE2I promotes metastasis and correlates with poor prognosis in hepatocellular carcinoma |
| title_sort | ube2i promotes metastasis and correlates with poor prognosis in hepatocellular carcinoma |
| topic | UBE2I Hepatocellular carcinoma Diagnosis Prognosis Migration Invasion |
| url | http://link.springer.com/article/10.1186/s12935-020-01311-x |
| work_keys_str_mv | AT haoyang ube2ipromotesmetastasisandcorrelateswithpoorprognosisinhepatocellularcarcinoma AT shangao ube2ipromotesmetastasisandcorrelateswithpoorprognosisinhepatocellularcarcinoma AT jingchen ube2ipromotesmetastasisandcorrelateswithpoorprognosisinhepatocellularcarcinoma AT weiyanglou ube2ipromotesmetastasisandcorrelateswithpoorprognosisinhepatocellularcarcinoma |