scholarly journals BAG2 promotes tumorigenesis through enhancing mutant p53 protein levels and function

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Xuetian Yue ◽  
Yuhan Zhao ◽  
Juan Liu ◽  
Cen Zhang ◽  
Haiyang Yu ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Growth ◽  
Poor Prognosis ◽  
P53 Protein ◽  
Underlying Mechanism ◽  
Mutant P53 ◽  
Tumor Suppressor P53 ◽  
Protein Levels ◽  
And Function

Tumor suppressor p53 is the most frequently mutated gene in tumors. Many mutant p53 (mutp53) proteins promote tumorigenesis through the gain-of-function (GOF) mechanism. Mutp53 proteins often accumulate to high levels in tumors, which is critical for mutp53 GOF. Its underlying mechanism is poorly understood. Here, we found that BAG2, a protein of Bcl-2 associated athanogene (BAG) family, promotes mutp53 accumulation and GOF in tumors. Mechanistically, BAG2 binds to mutp53 and translocates to the nucleus to inhibit the MDM2-mutp53 interaction, and MDM2-mediated ubiquitination and degradation of mutp53. Thus, BAG2 promotes mutp53 accumulation and GOF in tumor growth, metastasis and chemoresistance. BAG2 is frequently overexpressed in tumors. BAG2 overexpression is associated with poor prognosis in patients and mutp53 accumulation in tumors. These findings revealed a novel and important mechanism for mutp53 accumulation and GOF in tumors, and also uncovered an important role of BAG2 in tumorigenesis through promoting mutp53 accumulation and GOF.

scholarly journals Author response: BAG2 promotes tumorigenesis through enhancing mutant p53 protein levels and function

2015 ◽  
Author(s):  
Xuetian Yue ◽  
Yuhan Zhao ◽  
Juan Liu ◽  
Cen Zhang ◽  
Haiyang Yu ◽  
...  
Keyword(s):  
P53 Protein ◽  
Author Response ◽  
Mutant P53 ◽  
Protein Levels ◽  
And Function

scholarly journals A polymorphism in the tumor suppressor p53 affects aging and longevity in mouse models

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Yuhan Zhao ◽  
Lihua Wu ◽  
Xuetian Yue ◽  
Cen Zhang ◽  
Jianming Wang ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Development ◽  
Early Death ◽  
Tp53 Gene ◽  
Tumor Suppressor P53 ◽  
P53 Codon 72 ◽  
Codon 72 ◽  
And Function ◽  
Direct Genetic Evidence

Tumor suppressor p53 prevents early death due to cancer development. However, the role of p53 in aging process and longevity has not been well-established. In humans, single nucleotide polymorphism (SNP) with either arginine (R72) or proline (P72) at codon 72 influences p53 activity; the P72 allele has a weaker p53 activity and function in tumor suppression. Here, employing a mouse model with knock-in of human TP53 gene carrying codon 72 SNP, we found that despite increased cancer risk, P72 mice that escape tumor development display a longer lifespan than R72 mice. Further, P72 mice have a delayed development of aging-associated phenotypes compared with R72 mice. Mechanistically, P72 mice can better retain the self-renewal function of stem/progenitor cells compared with R72 mice during aging. This study provides direct genetic evidence demonstrating that p53 codon 72 SNP directly impacts aging and longevity, which supports a role of p53 in regulation of longevity.

scholarly journals Tumor suppressor p53 regulation and function

10.2741/a523 ◽  
2000 ◽  
Vol 5 (3) ◽  
pp. d424-437 ◽  
Author(s):  
Wafik S El-Deiry
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor P53 ◽  
And Function

scholarly journals Hypermethylation of DHRS3 as a Novel Tumor Suppressor Involved in Tumor Growth and Prognosis in Gastric Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Sha Sumei ◽  
Kong Xiangyun ◽  
Chen Fenrong ◽  
Sun Xueguang ◽  
Hu Sijun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Suppressor ◽  
Tumor Growth ◽  
Human Cancer ◽  
Methylation Status ◽  
Ectopic Expression ◽  
Survival Times

Background/AimsThe role of DHRS3 in human cancer remains unclear. Our study explored the role of DHRS3 in gastric cancer (GC) and its clinicopathological significance and associated mechanisms.MaterialsBisulfite-assisted genomic sequencing PCR and a Mass-Array system were used to evaluate and quantify the methylation levels of the promoter. The expression levels and biological function of DHRS3 was examined by both in vitro and in vivo assays. A two-way hierarchical cluster analysis was used to classify the methylation profiles, and the correlation between the methylation status of the DHRS3 promoter and the clinicopathological characteristics of GC were then assessed.ResultsThe DHRS3 promoter was hypermethylated in GC samples, while the mRNA and protein levels of DHRS3 were significantly downregulated. Ectopic expression of DHRS3 in GC cells inhibited cell proliferation and migration in vitro, decreased tumor growth in vivo. DHRS3 methylation was correlated with histological type and poor differentiation of tumors. GC patients with high degrees of CpG 9.10 methylation had shorter survival times than those with lower methylation.ConclusionDHRS3 was hypermethylated and downregulated in GC patients. Reduced expression of DHRS3 is implicated in gastric carcinogenesis, which suggests DHRS3 is a tumor suppressor.

scholarly journals Circular RNA hsa_circ_0043280 inhibits cervical cancer tumor growth and metastasis via miR-203a-3p/PAQR3 axis

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Chunyu Zhang ◽  
Pan Liu ◽  
Jiaming Huang ◽  
Yuandong Liao ◽  
Chaoyun Pan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Tumor Growth ◽  
Poor Prognosis ◽  
Prognostic Biomarker ◽  
Circular Rna ◽  
Circular Rnas ◽  
Inhibit Tumor Growth ◽  
Cancer Tumor ◽  
Tumor Growth And Metastasis

AbstractCircular RNAs (circRNAs) are known to act as key regulators in a variety of malignancies. However, the role of circRNAs in cervical cancer (CCa) remains largely unknown. Herein, we demonstrated that a circRNA derived from the TADA2A gene (hsa_circ_0043280) was significantly downregulated in CCa and that this reduction in expression was correlated with a poor prognosis. Furthermore, our results demonstrated that hsa_circ_0043280 functions as a tumor suppressor to inhibit tumor growth and metastasis in CCa. Mechanistically, hsa_circ_0043280 competitively sponges miR-203a-3p and prevents miR-203a-3p from reducing the levels of PAQR3. Collectively, our results demonstrate that hsa_circ_0043280 plays a pivotal role in the development and metastasis of CCa, thus suggesting that hsa_circ_0043280 has significant potential as a prognostic biomarker and a therapeutic target for CCa.

LncRNA GAS5 suppresses the proliferation and invasion of osteosarcoma cells via the miR-23a-3p/PTEN/PI3K/AKT pathway

2020 ◽  
Author(s):  
Jianmin Liu ◽  
Ming Chen ◽  
Longyang Ma ◽  
Xingbo Dang ◽  
Gongliang Du
Keyword(s):  
Tumor Suppressor ◽  
Tumor Growth ◽  
Akt Pathway ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Cell Behaviors ◽  
Human Osteosarcoma ◽  
Proliferation And Invasion

Abstract Background: Accumulating evidence has shown that lncRNA growth arrest special 5 (GAS5) is a well‑known tumor suppressor in the pathogenesis of a variety of human cancers. However, the detailed role of GAS5 in osteosarcoma is largely unclear. Here, we explore the role of GAS5 in progression of osteosarcoma. Methods: The expression level of GAS5 was detected in human osteosarcoma tissues and matched adjacent tissues, as well as osteosarcoma cell lines and non-malignant osteoblast cells. Then, in vitro gain- and loss-of-function experiments, with the pcDNA-GAS5 expression vector and GAS5-siRNA, were performed in U2OS and HOS cells to determine the effect of GAS5 on osteosarcoma cell proliferation and invasion. Subsequently, we searched potential miRNA targets with bioinformatics analysis and confirmed their interaction by using luciferase reporter gene and RNA pull-down assays. The function and mechanism of miR-23a-3p in proliferation and invasion was also investigated in U2OS and HOS cells. Furthermore, rescue experiments were performed to verify the involvement of miR-23a-3p and its target gene in GAS5-mediated cell behaviors. Finally, a xenograft nude mouse model was established by subcutaneous injection with U2OS cells overexpressing GAS5 or not, and the effect of GAS5 on tumor growth in vivo was evaluated. Results: GAS5 was downregulated in human osteosarcoma tissues and cell lines. Overexpression of GAS5 could significantly suppress, and downregulation of GAS5 promoted, proliferation and invasion of osteosarcoma cells. GAS5 could directly bind with and downregulated miR-23a-3p that post-transcriptionally downregulated the tumor suppressor PTEN and positively regulated proliferation and invasion of osteosarcoma cells. Rescue experiments confirmed the involvement of miR-23a-3p and PTEN in GAS5-mediated cell behaviors by modifying the phosphatidylinositol-3-kinases/protein-serine-threonine kinase (PI3K/AKT) pathway. GAS5 could inhibit tumor growth in vivo . Conclusion: GAS5 functions as a competing endogenous RNA , sponging miR-23a-3p, to promote PTEN expression and suppress cell growth and invasion in osteosarcoma by regulating the PI3K/AKT pathway.

scholarly journals Transcriptional Coactivator TAZ Negatively Regulates Tumor Suppressor p53 Activity and Cellular Senescence

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 171
Author(s):  
Chiharu Miyajima ◽  
Yuki Kawarada ◽  
Yasumichi Inoue ◽  
Chiaki Suzuki ◽  
Kana Mitamura ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Suppressor ◽  
Cellular Senescence ◽  
Hippo Pathway ◽  
Physiological Role ◽  
Underlying Mechanism ◽  
Binding Motif ◽  
Dependent Manner ◽  
Transcriptional Coactivator ◽  
Tumor Suppressor P53

Transcriptional coactivator with a PDZ-binding motif (TAZ) is one of the mammalian orthologs of Drosophila Yorkie, a transcriptional coactivator of the Hippo pathway. TAZ has been suggested to function as a regulator that modulates the expression of cell proliferation and anti-apoptotic genes in order to stimulate cell proliferation. TAZ has also been associated with a poor prognosis in several cancers, including breast cancer. However, the physiological role of TAZ in tumorigenesis remains unclear. We herein demonstrated that TAZ negatively regulated the activity of the tumor suppressor p53. The overexpression of TAZ down-regulated p53 transcriptional activity and its downstream gene expression. In contrast, TAZ knockdown up-regulated p21 expression induced by p53 activation. Regarding the underlying mechanism, TAZ inhibited the interaction between p53 and p300 and suppressed the p300-mediated acetylation of p53. Furthermore, TAZ knockdown induced cellular senescence in a p53-dependent manner. These results suggest that TAZ negatively regulates the tumor suppressor functions of p53 and attenuates p53-mediated cellular senescence.

scholarly journals The role of the tumor suppressor p53 in spermatogenesis

1998 ◽  
Vol 5 (8) ◽  
pp. 669-677 ◽  
Author(s):  
Tim L Beumer ◽  
Hermien L Roepers-Gajadien ◽  
Iris S Gademan ◽  
Paul PW van Buul ◽  
Gabriel Gil-Gomez ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor P53
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