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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Wang, Ming-Da Xing, Hao Li, Chao Liang, Lei Wu, Han Xu, Xin-Fei Sun, Li-Yang Wu, Meng-Chao Shen, Feng Yang, Tian |
| Abstract | Background Krüppel-like factor 8 (KLF8), a cancer-promoting factor that regulates critical gene transcription and cellular cancer-related events, has been implicated in tumor development and progression. However, the functional role of KLF8 in the pathogenesis of hepatocellular carcinoma (HCC) remains largely unknown. Methods The gene expression patterns and genome-wide regulatory profiles of HCC cells after KLF8 knockout were analyzed by using RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) of histone H3 lysine 27 acetylation (H3K27ac) combined with bioinformatics analysis. Transcription factor-binding motifs that recognized by KLF8 were evaluated by motif analysis. For the predicted target genes, transcriptional changes were examined by ChIP, and loss of function experiments were conducted by siRNA transfection. Results KLF8 functioned as a transcription repressor in HCC and mainly regulated apoptotic-related genes directly. A total of 1,816 differentially expressed genes after KLF8 knockout were identified and significantly corresponded to global changes in H3K27ac status. Furthermore, two predicted target genes, high-mobility group AT-hook 2 (HMGA2) and matrix metalloproteinase 7 (MMP7), were identified as important participants in KLF8-mediated anti-apoptotic effect in HCC. Knockout of KLF8 enhanced cell apoptosis process and caused increase in the associated H3K27ac, whereas suppression HMGA2 or MMP7 attenuated these biological effects. Conclusions Our work suggests a novel role and mechanism for KLF8 in the regulation of cell apoptosis in HCC and facilitates the discovery of potential therapeutic targets for HCC treatment. |
| Related Links | https://cancerci.biomedcentral.com/counter/pdf/10.1186/s12935-020-01513-3.pdf |
| Ending Page | 12 |
| Page Count | 12 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14752867 |
| DOI | 10.1186/s12935-020-01513-3 |
| Journal | Cancer Cell International |
| Issue Number | 1 |
| Volume Number | 20 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2020-08-28 |
| Access Restriction | Open |
| Subject Keyword | Cancer Research Cell Biology Hepatocellular carcinoma KLF8 Apoptosis H3K27 acetylation HMGA2 MMP7 |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Genetics Oncology |
| Journal Impact Factor | 5.3/2023 |
| 5-Year Journal Impact Factor | 5/2023 |
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