DTX2 promotes glioma development via regulation of HLTF
© 2023. The Author(s)..
BACKGROUND: Human Deltex 2 (DTX2) is a ubiquitin E3 ligase that functions as an oncogene and has been shown to participate in many human cancers. However, the role of DTX2 in glioma progression has remained obscure. In this study, we explore the mechanism underlying the function of DTX2 in glioma progression.
METHODS: The associations between DTX2 expression and clinical characteristics of glioma were determined by bioinformatic analysis of data from The Cancer Genome Atlas and Human Protein Atlas. The expression of DTX2 in glioma tissues was detected using immunohistochemistry and western blotting. Lentivirus-mediated gene knockdown and overexpression were used to determine the effects of DTX2 and helicase-like transcription element (HLTF) on glioma cell proliferation and migration with CCK-8, cell colony formation, transwell, and wound healing assays; flow cytometry in vitro; and animal models in vivo. The interaction of the DTX2 and HLTF proteins was verified by immunoprecipitation assay and confocal microscopy.
RESULTS: DTX2 was highly expressed in glioma samples, and this was correlated with worse overall survival. Silencing of DTX2 suppressed glioma cell viability, colony formation, and migration and induced cell apoptosis. In vitro ubiquitination assays confirmed that DTX2 could downregulate HLTF protein levels by increasing ubiquitination of the HLTF protein. We also observed that HLTF inhibited proliferation and migration of glioma cells. Subcutaneous xenografts with DTX2-overexpressing U87 cells showed significantly increased tumor volumes and weights.
CONCLUSIONS: We have identified DTX2/HLTF as a new axis in the development of glioma that could serve as a prognostic or therapeutic marker.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
|---|---|
| Enthalten in: |
Biology direct - 19(2024), 1 vom: 02. Jan., Seite 2 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Li, Ren [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
DNA-Binding Proteins |
|---|
| Anmerkungen: |
Date Completed 03.01.2024 Date Revised 04.01.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1186/s13062-023-00447-w |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM36654537X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM36654537X | ||
| 003 | DE-627 | ||
| 005 | 20240108141801.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240108s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s13062-023-00447-w |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1248.xml |
| 035 | |a (DE-627)NLM36654537X | ||
| 035 | |a (NLM)38163902 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Li, Ren |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a DTX2 promotes glioma development via regulation of HLTF |
| 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 03.01.2024 | ||
| 500 | |a Date Revised 04.01.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a BACKGROUND: Human Deltex 2 (DTX2) is a ubiquitin E3 ligase that functions as an oncogene and has been shown to participate in many human cancers. However, the role of DTX2 in glioma progression has remained obscure. In this study, we explore the mechanism underlying the function of DTX2 in glioma progression | ||
| 520 | |a METHODS: The associations between DTX2 expression and clinical characteristics of glioma were determined by bioinformatic analysis of data from The Cancer Genome Atlas and Human Protein Atlas. The expression of DTX2 in glioma tissues was detected using immunohistochemistry and western blotting. Lentivirus-mediated gene knockdown and overexpression were used to determine the effects of DTX2 and helicase-like transcription element (HLTF) on glioma cell proliferation and migration with CCK-8, cell colony formation, transwell, and wound healing assays; flow cytometry in vitro; and animal models in vivo. The interaction of the DTX2 and HLTF proteins was verified by immunoprecipitation assay and confocal microscopy | ||
| 520 | |a RESULTS: DTX2 was highly expressed in glioma samples, and this was correlated with worse overall survival. Silencing of DTX2 suppressed glioma cell viability, colony formation, and migration and induced cell apoptosis. In vitro ubiquitination assays confirmed that DTX2 could downregulate HLTF protein levels by increasing ubiquitination of the HLTF protein. We also observed that HLTF inhibited proliferation and migration of glioma cells. Subcutaneous xenografts with DTX2-overexpressing U87 cells showed significantly increased tumor volumes and weights | ||
| 520 | |a CONCLUSIONS: We have identified DTX2/HLTF as a new axis in the development of glioma that could serve as a prognostic or therapeutic marker | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a DTX2 | |
| 650 | 4 | |a Glioma | |
| 650 | 4 | |a HLTF | |
| 650 | 4 | |a Ubiquitination | |
| 650 | 7 | |a dinophysistoxin 2 |2 NLM | |
| 650 | 7 | |a RH78DHY1JZ |2 NLM | |
| 650 | 7 | |a HLTF protein, human |2 NLM | |
| 650 | 7 | |a DNA-Binding Proteins |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 700 | 1 | |a Chen, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Biao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ziao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Peize |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jiayu |e verfasserin |4 aut | |
| 700 | 1 | |a He, Jianhang |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yongqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Yanqi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiaogang |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Xiaolong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wenju |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yuanli |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Geng |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Biology direct |d 2006 |g 19(2024), 1 vom: 02. Jan., Seite 2 |w (DE-627)NLM161320317 |x 1745-6150 |7 nnns |
| 773 | 1 | 8 | |g volume:19 |g year:2024 |g number:1 |g day:02 |g month:01 |g pages:2 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1186/s13062-023-00447-w |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 19 |j 2024 |e 1 |b 02 |c 01 |h 2 | ||