Transcription factor KLF9 suppresses the growth of hepatocellular carcinoma cells in vivo and positively regulates p53 expression
Abstract
Krüppel-like factor 9 (KLF9) is known to be a tumor suppressor gene in colorectal tumors and glioblastoma; however, the functional status and significance of KLF9 in hepatocellular carcinoma (HCC) is unclear. We report here that KLF9 is downregulated in HCC tissues. Restoration of KLF9 significantly inhibited growth and caused apoptosis in SK-Hep1 and HepG2 cells. We found that KLF9 positively regulated p53 levels by directly binding to GC boxes within the proximal region of the p53 promoter. Moreover, in the presence of cycloheximide, KLF9 significantly increased p53 stability in HCC cells. Remarkably, ectopic expression of KLF9 was sufficient to delay the onset of tumors and to promote regression of the established tumors in vivo, suggesting that KLF9 plays a critical role in HCC development and that pharmacological or genetic activation of KLF9 may have potential in the treatment of HCC.
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Overexpression or activation of several Hep-IDCONNECT transcription factors, GATA6, KLF9, TBX3, NR1H3, and THRB, has been shown to suppress hepatocarcinogenesis.
“overexpression or activation of several Hep‐IDCONNECT TFs, GATA‐binding protein 6 (GATA6), krüppel‐like factor 9 (KLF9), T‐box transcription factor 3 (TBX3) and the nuclear receptors liver X receptor alpha (NR1H3 also known as LXR alpha) and thyroid hormone receptor beta (THRB), has been shown to suppress hepatocarcinogenesis (Fig 4C; Sun et al, 2014; Tan et al, 2019; Kowalik et al, 2020; Lin et a”
From An extended transcription factor regulatory network controls hepatocyte identity (2023) · cites this paper as Sun et al, 2014
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An extended transcription factor regulatory network controls hepatocyte identity
Dubois‐Chevalier, J., Gheeraert, C., Berthier, A., Boulet, C., Dubois, V., Guille, L., Fourcot, M., Marot, G., Gauthier, K., Dubuquoy, L., et al. (2023) · EMBO Reports · doi:10.15252/embr.202357020 · Cited by 6 · see citing works
- Authors
- Sun, J., Wang, B., Liu, Y., Zhang, L., Ma, A., Yang, Z., Ji, Y., & Liu, Y.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Venue
- Cancer Letters
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 355
- Issue
- 1
- Pages
- 25-33
- ISSN
- 0304-3835 (ISSN-L)
- OpenAlex
- W2050403676
- Cited by
- 83
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 18 · 2023: 12 · 2022: 9 · 2021: 12 · 2020: 10 · 2019: 7 · 2018: 5 · 2017: 2 · 2016: 3 · 2015: 1
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation of China (81201542, 81301716)
- Natural Science Foundation of Shanghai (12ZR1430100)
- Key Discipline and Specialty Foundation of Shanghai Municipal Commission of Health and Family Planning
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- KLF9, hepatocellular carcinoma, tumor suppressor, p53 expression, p53 promoter, p53 stabilization, apoptosis, tumor growth inhibition, tumor regression, transcription factors
- MeSH terms
- Animals, Binding Sites, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Mice, Inbred BALB C, Mice, Nude, Promoter Regions, Genetic, Time Factors, Transcription, Genetic, Transfection, Signal Transduction, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53, Apoptosis, Cell Proliferation, Kruppel-Like Transcription Factors, Protein Stability, Hep G2 Cells
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