HNF1A induces glioblastoma by upregulating EPS8 and activating PI3K/AKT signaling pathway
Copyright © 2024 Elsevier Inc. All rights reserved..
Despite the exact biological role of HNF1 homolog A (HNF1A) in the regulatory mechanism of glioblastoma (GBM), the molecular mechanism, especially the downstream regulation as a transcription factor, remains to be further elucidated. Immunohistochemistry was used to detect the expression and clinical relevance of HNF1A in GBM patients. CCK8, TUNEL, and subcutaneous tumor formation in nude mice were used to evaluate the effect of HNF1A on GBM in vitro and in vivo. The correction between HNF1A and epidermal growth factor receptor pathway substrate 8 (EPS8) was illustrated by bioinformatics analysis and luciferase assay. Further mechanism was explored that the transcription factor HNF1A regulated the expression of EPS8 and downstream signaling pathways by directly binding to the promoter region of EPS8. Our comprehensive analysis of clinical samples in this study showed that upregulated expression of HNF1A was associated with poor survival in GBM patients. Further, we found that knockdown of HNF1A markedly suppressed the malignant phenotype of GBM cells in vivo and in vitro as well as promoted apoptosis of tumor cells, which was reversed by upregulation of HNF1A. Mechanistically, HNF1A could significantly activate PI3K/AKT signaling pathway by specifically binding to the promoter regions of EPS8. Moreover, overexpression of EPS8 was able to reverse the apoptosis of tumor cells caused by HNF1A knockdown, thereby exacerbating the GBM progression. Correctively, our study has clarified the explicit mechanism by which HNF1A promotes GBM malignancy and provides a new therapeutic target for further clinical application.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:223 |
|---|---|
| Enthalten in: |
Biochemical pharmacology - 223(2024) vom: 15. Apr., Seite 116133 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Yang, Gang [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 22.04.2024 Date Revised 22.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.bcp.2024.116133 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM36983755X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM36983755X | ||
| 003 | DE-627 | ||
| 005 | 20240422232239.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240318s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.bcp.2024.116133 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1383.xml |
| 035 | |a (DE-627)NLM36983755X | ||
| 035 | |a (NLM)38494066 | ||
| 035 | |a (PII)S0006-2952(24)00116-3 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Yang, Gang |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a HNF1A induces glioblastoma by upregulating EPS8 and activating PI3K/AKT signaling pathway |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 22.04.2024 | ||
| 500 | |a Date Revised 22.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier Inc. All rights reserved. | ||
| 520 | |a Despite the exact biological role of HNF1 homolog A (HNF1A) in the regulatory mechanism of glioblastoma (GBM), the molecular mechanism, especially the downstream regulation as a transcription factor, remains to be further elucidated. Immunohistochemistry was used to detect the expression and clinical relevance of HNF1A in GBM patients. CCK8, TUNEL, and subcutaneous tumor formation in nude mice were used to evaluate the effect of HNF1A on GBM in vitro and in vivo. The correction between HNF1A and epidermal growth factor receptor pathway substrate 8 (EPS8) was illustrated by bioinformatics analysis and luciferase assay. Further mechanism was explored that the transcription factor HNF1A regulated the expression of EPS8 and downstream signaling pathways by directly binding to the promoter region of EPS8. Our comprehensive analysis of clinical samples in this study showed that upregulated expression of HNF1A was associated with poor survival in GBM patients. Further, we found that knockdown of HNF1A markedly suppressed the malignant phenotype of GBM cells in vivo and in vitro as well as promoted apoptosis of tumor cells, which was reversed by upregulation of HNF1A. Mechanistically, HNF1A could significantly activate PI3K/AKT signaling pathway by specifically binding to the promoter regions of EPS8. Moreover, overexpression of EPS8 was able to reverse the apoptosis of tumor cells caused by HNF1A knockdown, thereby exacerbating the GBM progression. Correctively, our study has clarified the explicit mechanism by which HNF1A promotes GBM malignancy and provides a new therapeutic target for further clinical application | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a EPS8 | |
| 650 | 4 | |a GBM | |
| 650 | 4 | |a HNF1A | |
| 650 | 4 | |a PI3K/AKT signaling pathway | |
| 650 | 4 | |a Transcriptional regulation | |
| 650 | 7 | |a Proto-Oncogene Proteins c-akt |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Phosphatidylinositol 3-Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.1.- |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 650 | 7 | |a HNF1A protein, human |2 NLM | |
| 650 | 7 | |a Hepatocyte Nuclear Factor 1-alpha |2 NLM | |
| 650 | 7 | |a EPS8 protein, human |2 NLM | |
| 650 | 7 | |a Adaptor Proteins, Signal Transducing |2 NLM | |
| 700 | 1 | |a Su, Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Bin-Xiao |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Hong-Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Chen-Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Shao-Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Guan, Quan-Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Xiao-Ming |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Biochemical pharmacology |d 1959 |g 223(2024) vom: 15. Apr., Seite 116133 |w (DE-627)NLM000000094 |x 1873-2968 |7 nnns |
| 773 | 1 | 8 | |g volume:223 |g year:2024 |g day:15 |g month:04 |g pages:116133 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.bcp.2024.116133 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 223 |j 2024 |b 15 |c 04 |h 116133 | ||