Article ; Online: Transcription Factor E2F1 Enhances Hepatocellular Carcinoma Cell Proliferation and Stemness by Activating GINS1.
2023 Volume 43, Issue 1, Page(s) 79–90
Abstract: Present studies report that high expression of GINS complex subunit 1 (GINS1) is notably pertinent to poor survival for hepatocellular carcinoma (HCC), but it remains unclear how GINS1 affects the progression of HCC. This study aims at investigating the ... ...
| Abstract | Present studies report that high expression of GINS complex subunit 1 (GINS1) is notably pertinent to poor survival for hepatocellular carcinoma (HCC), but it remains unclear how GINS1 affects the progression of HCC. This study aims at investigating the mechanism by which GINS1 affects HCC cell proliferation and stemness. We performed bioinformatics analysis for determining GINS1 expression in HCC tissues, as well as the HCC patients' survival rate with different expression levels of GINS1. E2F transcription factor 1 (E2F1) was predicted as the upstream transcription factor of GINS1, and the binding relation between the two was verified by chromatin immunoprecipitation and dual-luciferase reporter assays. Quantitative real-time polymerase chain reaction was adopted to evaluate the expression of GINS1 and E2F1. The protein expression levels of GINS1, E2F1, and cell stemness-related genes (SOX-2, NANOG, OCT4, and CD133) were detected by Western blot. Afterward, the proliferative capacity and stemness of HCC tumor cells were determined through colony formation, cell counting kit-8, and sphere formation assays. Our study found the high expression of GINS1 and E2F1 in HCC, and overexpressed GINS1 markedly enhanced the sphere formation and proliferation of HCC cells, while silencing GINS1 led to the opposite results. Besides, E2F1 promoted the transcription of GINS1 by working as an upstream transcription factor. The results of the rescue experiment suggested that overexpressed E2F1 could offset the suppressive effect of GINS1 silencing on HCC cell stemness and proliferation. We demonstrated that the transcription factor E2F1 accelerated cell proliferation and stemness in HCC by activating GINS1 transcription. The results can provide new insight into the GINS1-related regulatory mechanism in HCC, which suggest that it may be an effective way for HCC treatment by targeting the E2F1/GINS1 axis. |
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| MeSH term(s) | Humans ; Carcinoma, Hepatocellular/pathology ; Liver Neoplasms/metabolism ; E2F1 Transcription Factor/genetics ; E2F1 Transcription Factor/metabolism ; Cell Line, Tumor ; Cell Proliferation/genetics ; Gene Expression Regulation, Neoplastic ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism |
| Chemical Substances | E2F1 Transcription Factor ; E2F1 protein, human ; GINS1 protein, human ; DNA-Binding Proteins |
| Language | English |
| Publishing date | 2023-09-30 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 441790-2 |
| ISSN | 2162-6537 ; 0731-8898 ; 0146-4779 |
| ISSN (online) | 2162-6537 |
| ISSN | 0731-8898 ; 0146-4779 |
| DOI | 10.1615/JEnvironPatholToxicolOncol.2023048594 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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