AURKB promotes bladder cancer progression by deregulating the p53 DNA damage response pathway via MAD2L2
© 2024. The Author(s)..
BACKGROUND: Bladder cancer (BC) is the most common urinary tract malignancy. Aurora kinase B (AURKB), a component of the chromosomal passenger protein complex, affects chromosomal segregation during cell division. Mitotic arrest-deficient 2-like protein 2 (MAD2L2) interacts with various proteins and contributes to genomic integrity. Both AURKB and MAD2L2 are overexpressed in various human cancers and have synergistic oncogenic effects; therefore, they are regarded as emerging therapeutic targets for cancer. However, the relationship between these factors and the mechanisms underlying their oncogenic activity in BC remains largely unknown. The present study aimed to explore the interactions between AURKB and MAD2L2 and how they affect BC progression via the DNA damage response (DDR) pathway.
METHODS: Bioinformatics was used to analyze the expression, prognostic value, and pro-tumoral function of AURKB in patients with BC. CCK-8 assay, colony-forming assay, flow cytometry, SA-β-gal staining, wound healing assay, and transwell chamber experiments were performed to test the viability, cell cycle progression, senescence, and migration and invasion abilities of BC cells in vitro. A nude mouse xenograft assay was performed to test the tumorigenesis ability of BC cells in vivo. The expression and interaction of proteins and the occurrence of the senescence-associated secretory phenotype were detected using western blot analysis, co-immunoprecipitation assay, and RT-qPCR.
RESULTS: AURKB was highly expressed and associated with prognosis in patients with BC. AURKB expression was positively correlated with MAD2L2 expression. We confirmed that AURKB interacts with, and modulates the expression of, MAD2L2 in BC cells. AURKB knockdown suppressed the proliferation, migration, and invasion abilities of, and cell cycle progression in, BC cells, inducing senescence in these cells. The effects of AURKB knockdown were rescued by MAD2L2 overexpression in vitro and in vivo. The effects of MAD2L2 knockdown were similar to those of AURKB knockdown. Furthermore, p53 ablation rescued the MAD2L2 knockdown-induced suppression of BC cell proliferation and cell cycle arrest and senescence in BC cells.
CONCLUSIONS: AURKB activates MAD2L2 expression to downregulate the p53 DDR pathway, thereby promoting BC progression. Thus, AURKB may serve as a potential molecular marker and a novel anticancer therapeutic target for BC.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
|---|---|
| Enthalten in: |
Journal of translational medicine - 22(2024), 1 vom: 21. März, Seite 295 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Li, Linzhi [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 27.03.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1186/s12967-024-05099-6 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370046854 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370046854 | ||
| 003 | DE-627 | ||
| 005 | 20240328000256.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240323s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s12967-024-05099-6 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1351.xml |
| 035 | |a (DE-627)NLM370046854 | ||
| 035 | |a (NLM)38515112 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Li, Linzhi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a AURKB promotes bladder cancer progression by deregulating the p53 DNA damage response pathway via MAD2L2 |
| 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 25.03.2024 | ||
| 500 | |a Date Revised 27.03.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a BACKGROUND: Bladder cancer (BC) is the most common urinary tract malignancy. Aurora kinase B (AURKB), a component of the chromosomal passenger protein complex, affects chromosomal segregation during cell division. Mitotic arrest-deficient 2-like protein 2 (MAD2L2) interacts with various proteins and contributes to genomic integrity. Both AURKB and MAD2L2 are overexpressed in various human cancers and have synergistic oncogenic effects; therefore, they are regarded as emerging therapeutic targets for cancer. However, the relationship between these factors and the mechanisms underlying their oncogenic activity in BC remains largely unknown. The present study aimed to explore the interactions between AURKB and MAD2L2 and how they affect BC progression via the DNA damage response (DDR) pathway | ||
| 520 | |a METHODS: Bioinformatics was used to analyze the expression, prognostic value, and pro-tumoral function of AURKB in patients with BC. CCK-8 assay, colony-forming assay, flow cytometry, SA-β-gal staining, wound healing assay, and transwell chamber experiments were performed to test the viability, cell cycle progression, senescence, and migration and invasion abilities of BC cells in vitro. A nude mouse xenograft assay was performed to test the tumorigenesis ability of BC cells in vivo. The expression and interaction of proteins and the occurrence of the senescence-associated secretory phenotype were detected using western blot analysis, co-immunoprecipitation assay, and RT-qPCR | ||
| 520 | |a RESULTS: AURKB was highly expressed and associated with prognosis in patients with BC. AURKB expression was positively correlated with MAD2L2 expression. We confirmed that AURKB interacts with, and modulates the expression of, MAD2L2 in BC cells. AURKB knockdown suppressed the proliferation, migration, and invasion abilities of, and cell cycle progression in, BC cells, inducing senescence in these cells. The effects of AURKB knockdown were rescued by MAD2L2 overexpression in vitro and in vivo. The effects of MAD2L2 knockdown were similar to those of AURKB knockdown. Furthermore, p53 ablation rescued the MAD2L2 knockdown-induced suppression of BC cell proliferation and cell cycle arrest and senescence in BC cells | ||
| 520 | |a CONCLUSIONS: AURKB activates MAD2L2 expression to downregulate the p53 DDR pathway, thereby promoting BC progression. Thus, AURKB may serve as a potential molecular marker and a novel anticancer therapeutic target for BC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Aurora kinase B | |
| 650 | 4 | |a Bladder cancer | |
| 650 | 4 | |a Mitotic arrest-deficient 2-like protein 2 | |
| 650 | 4 | |a p53 | |
| 650 | 7 | |a AURKB protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Aurora Kinase B |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Mad2 Proteins |2 NLM | |
| 650 | 7 | |a MAD2L2 protein, human |2 NLM | |
| 650 | 7 | |a Tumor Suppressor Protein p53 |2 NLM | |
| 650 | 7 | |a TP53 protein, human |2 NLM | |
| 700 | 1 | |a Jiang, Pengcheng |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Weimin |e verfasserin |4 aut | |
| 700 | 1 | |a Zou, Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Rao, Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Ruan, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Weimin |e verfasserin |4 aut | |
| 700 | 1 | |a Ning, Jinzhuo |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Fan |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of translational medicine |d 2003 |g 22(2024), 1 vom: 21. März, Seite 295 |w (DE-627)NLM142679194 |x 1479-5876 |7 nnns |
| 773 | 1 | 8 | |g volume:22 |g year:2024 |g number:1 |g day:21 |g month:03 |g pages:295 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1186/s12967-024-05099-6 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 22 |j 2024 |e 1 |b 21 |c 03 |h 295 | ||