Hypoxia but not normoxia promotes Smoothened transcription through upregulation of RBPJ and Mastermind-like 3 in pancreatic cancer

Onishi, Hideya; Yamasaki, Akio; Kawamoto, Makoto; Imaizumi, Akira; Katano, Mitsuo

doi:10.1016/j.canlet.2015.11.012

Cited by 27 publications

(25 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, functional study on MAML3 is limited. Studies have shown that MAML3 overexpression may be involved in cancer metastasis (25), suggesting that MAML3 overexpression was associated with poor prognosis, which was discordant with our results. It implied that MAML3 may involve other regulatory and oncogenic mechanisms in DLBCL.…”

Section: Mybl1 Maml3supporting

confidence: 69%

Subtype classification and prognosis of diffuse large B-cell lymphoma based on variable importance analysis

Gao

Zhang

Que

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Gene expression profiling (GEP) is considered as gold standard for cell-of-origin classification of diffuse large B-cell lymphoma (DLBCL). The high dimensionality of GEP limits its application in clinical practice. Penalized regression was commonly used to determine the optimal gene subset for classification in high dimensional gene data. However, the results of penalized regression methods were affected by the tuning parameters.Results To solve the instability of penalized regression methods, we proposed a strategy to measure the importance of variables with an aggregated index. This strategy was applied to six penalized methods to identify a small gene subset for DLBCL classification. Using a training dataset of 350 DLBCL patients, we identified six genes (MYBL1, TNFRSF13B, MAML3, CYB5R2, BATF, and S1PR2) as the optimal gene subset for DLBCL classification. The AUC was 0.9986 (95%CI 0.9967–1) and discrimination slope (DS) was 0.9442 (95%CI 0.9203–0.9661) in the training dataset. The discriminative performances were further validated in the external dataset with an AUC of 0.9455 (95%CI 0.9298–0.9612) and DS of 0.6211 (95%CI 0.5824–0.6591). Additionally, the calibration and clinical usefulness were apt in both datasets. Subgroups of patients characterized by these six genes showed significantly different prognosis. Furthermore, model comparisons demonstrated that the six-gene model outperformed models constructed by typical penalized regression methods.Conclusions The six genes had considerable clinical usefulness in DLBCL classification and prognosis. Penalized variable importance analysis is an efficient strategy to identify an optimal gene subset with good predictive performance.

show abstract

Section: Mybl1 Maml3supporting

confidence: 69%

Subtype classification and prognosis of diffuse large B-cell lymphoma based on variable importance analysis

Gao

Zhang

Que

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…A recent report suggests that miR-133a-3p downregulates RBPJ expression to inhibit the tumorigenic properties (33). RBPJ has also been reported to be induced under hypoxic conditions (34). However, the mechanism of RBPJ induction under hypoxic conditions remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Cyclin F-Dependent Degradation of RBPJ Inhibits IDH1R132H-Mediated Tumorigenesis

2018

View full text Add to dashboard Cite

Cyclin F is a substrate recognition subunit of Skp1-Cul1-Fbox protein (SCF) E3 ubiquitin ligase complex. Although there have been reports describing the role of cyclin F in the genotoxic stress response, its function under conditions of altered metabolic homeostasis remain unexplored. Here we report that cyclin F is induced upon metabolic stress in a FOXO1-dependent manner. Under metabolic stress conditions, cyclin F mediated polyubiquitylation of RBPJ at Lys315, leading to its proteasomal degradation. RBPJ regulated the expression of IDH1, which is often mutated to an oncogenic form IDH1 R132H in cancers. Thus, metabolic stress-induced cyclin F attenuated the oncogenic functions of IDH1 R132H in an RBPJ-dependent manner. Studies in mouse tumor models indicated that abrogation of cyclin F expression facilitates IDH1 R132H -mediated tumorigenesis and metastasis. In addition, increased IDH1 R132H levels correlated with reduced cyclin F levels in increasing grades of glioma. These findings highlight a novel aspect of cyclin F functions in inhibiting tumorigenesis and provide mechanistic insights into regulation of IDH1 R132H .Significance: These findings reveal mechanistic insights into the key role of the cyclin F-RBPJ axis in response to metabolic stress in cancer cells. Cancer Res; 78 (22); 6386-98. Ó2018 AACR.

show abstract

“…Together with the Notch intracellular domain and the DNA‐binding protein CSL, MAML forms a transcriptional complex to drive expression of Notch target genes (31, 32). MAML3 has been described as an oncogene, and MAML3 up‐regulation induced by hypoxia promotes the proliferation and invasion of pancreatic cancer (33). In addition, microarray data reported by Vasko et al (34) showed that MAML3 is overexpressed in invasive fronts compared to that of central regions of primary papillary thyroid carcinoma, suggesting its involvement in cancer metastasis.…”

Section: Discussionmentioning

confidence: 99%

MiR‐2392 suppresses metastasis and epithelial–mesenchymal transition by targeting MAML3 and WHSC1 in gastric cancer

et al. 2017

FASEB j.

View full text Add to dashboard Cite

MicroRNAs have emerged as essential regulators of various cellular processes. We identified the role and underlying mechanisms of miR-2392 in gastric cancer (GC) metastasis. MiR-2392 was down-regulated in GC cell lines and tissues, and overexpression of miR-2392 significantly inhibited GC invasion and metastasis and We identified and as novel targets of miR-2392, and knockdown of MAML3 and WHSC1 had the same antimetastatic effect as that of miR-2392 in GC cells. These effects were clinically relevant, as low miR-2392 expression was correlated with high MAML3 and WHSC1 expression and poor survival in patients with GC. Furthermore, forced expression of miR-2392 substantially suppressed Slug and Twist1, transcriptional repressors of E-cadherin, by targeting and, respectively, resulting in inhibition of the epithelial-mesenchymal transition. These findings indicate that the miR-2392-/-/ regulatory axis plays a critical role in GC metastasis. Restoration of miR-2392 may be a therapeutic approach for blocking GC metastasis.-Li, J., Li, T., Lu, Y., Shen, G., Guo, H., Wu, J., Lei, C., Du, F., Zhou, F., Zhao, X., Nie, Y., Fan, D. MiR-2392 suppresses metastasis and epithelial-mesenchymal transition by targeting and in gastric cancer.

show abstract

Hypoxia but not normoxia promotes Smoothened transcription through upregulation of RBPJ and Mastermind-like 3 in pancreatic cancer

Cited by 27 publications

References 18 publications

Subtype classification and prognosis of diffuse large B-cell lymphoma based on variable importance analysis

Subtype classification and prognosis of diffuse large B-cell lymphoma based on variable importance analysis

Cyclin F-Dependent Degradation of RBPJ Inhibits IDH1R132H-Mediated Tumorigenesis

MiR‐2392 suppresses metastasis and epithelial–mesenchymal transition by targeting MAML3 and WHSC1 in gastric cancer

Contact Info

Product

Resources

About