Phosphomevalonate Kinase Controls <i>β</i>‐Catenin Signaling via the Metabolite 5‐Diphosphomevalonate

Chen, Zhiqiang; Zhou, Xinyi; Zhou, Xiaojun; Tang, Yi; Lu, Mingzhu; Zhao, Jingbo; Tian, Chenhui; Wu, Mingzhi; Liu, Yanliang; Prochownik, Edward V.; Wang, Xinghuan; Li, Youjun

doi:10.1002/advs.202204909

Cited by 4 publications

(2 citation statements)

References 50 publications

(58 reference statements)

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“…In 1 mL of lysis buffer (50 mm Tris base (pH 7.4), 150 mm Sodium chloride, 1% Nonidet P‐40, 0.5% sodium deoxycholate, 0.1% Sodium dodecyl sulfate, 5 mm Ethylene Diamine Tetraacetic Acid and 1 mm benzylsulfonyl fluoride), the transfected accordingly KIRC cells were lysed. Immunoblot analysis were performed as described 12 …”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, the drug XAV939 with the most significant difference was a clinically widely used inhibitor of wntβ-catenin, a signaling pathway that is aberrantly activated in tumors. TTN [16] BAP1 [12] MUC16 [ 8] PKHD1 [ 7] GPR179 [ 6] KDM5C [ 6] MED13 [ 6] MYCBP2 [ 6] SETD2 [ 6] AHNAK2 [ 5] CSMD3 [ 5] FBN2 [ 5] LYST [ 5] PCDH15 [ 5] PCLO [ 5] SMARCA4 [ 5] ZMYM2 [ 5] NUP210L KMT2C [ 9] ARID1A [ 8] ANK3 [ 6] ATM [ 6] BAZ1B [ 6] DNAH5 [ 6] ERBB4 [ 6] IFT140 [ 6] LRP2 [ 6] MUC16 [ 6] SETD2 [ 6] USH2A [ 6] UTRN [ 6] ABCA12 [ 5] AHNAK2 [ 5] ATF7IP2 [ 5] BAP1…”

Section: Prediction Of the Chemotherapy Response Sensitivitymentioning

confidence: 99%

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Genes associated with N6‐methyladenosine regulators provide insight into the prognosis and immune response to renal clear cell carcinoma

Fan

Wang

et al. 2023

Environmental Toxicology

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As one of the most common messenger ribonucleic acid modifications in eukaryotic organisms, N6‐methyladenosine (m6A) is involved in a wide variety of biological functions. The imbalance of m6A RNA modification may be linked to cancer and other disorders, according to a growing body of studies. Its effects on clear cell renal cell carcinoma (KIRC) have not been well discussed, though. Here, we acquired the expression patterns of 23 important regulators of m6A RNA modification and assess how they might fare in KIRC. We observed that 17 major m6A RNA modification regulatory factors had a substantial predictive influence on KIRC. Using the “ConsensusCluster” program, we defined two groupings (Cluster 1 and Cluster 2) depending on the expression of the aforementioned 17 key m6A RNA methylation regulators. The Cluster 2 has a less favorable outcome and is strongly related with a lesser immune microenvironment, according to the findings. We also developed a strong risk profile for three m6A RNA modifiers (METTL14, YTHDF1, and LRPPRC) using multivariate Cox regression analysis. According to further research, the aforementioned risk profile could serve as an independent predicting factor for KIRC, and the chemotherapy response sensitivity was analyzed between two risk groups. Moreover, to effectively forecast the future outlook of KIRC clients, we established a novel prognostic approach according to gender, age, histopathological level, clinical stage, and risk score. Finally, the function of hub gene METTL14 was validated by cell proliferation and subcutaneous graft tumor in mice. In conclusion, we discovered that m6A RNA modifiers play an important role in controlling KIRC and created a viable risk profile as a marker of prediction for KIRC clients.

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Section: Methodsmentioning

confidence: 99%

Section: Prediction Of the Chemotherapy Response Sensitivitymentioning

confidence: 99%

Genes associated with N6‐methyladenosine regulators provide insight into the prognosis and immune response to renal clear cell carcinoma

Fan

Wang

et al. 2023

Environmental Toxicology

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Phosphomevalonate Kinase Controls β‐Catenin Signaling via the Metabolite 5‐Diphosphomevalonate

Chen

Zhou

et al. 2023

Advanced Science

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β‐catenin signaling is abnormally activated in cancer. Here, this work screens the mevalonate metabolic pathway enzyme PMVK to stabilize β‐catenin signaling using a human genome‐wide library. On the one hand, PMVK‐produced MVA‐5PP competitively binds to CKIα to prevent β‐catenin Ser45 phosphorylation and degradation. On the other hand, PMVK functions as a protein kinase to directly phosphorylate β‐catenin Ser184 to increase its protein nuclear localization. This synergistic effect of PMVK and MVA‐5PP together promotes β‐catenin signaling. In addition, PMVK deletion impairs mouse embryonic development and causes embryonic lethal. PMVK deficiency in liver tissue alleviates DEN/CCl4‐induced hepatocarcinogenesis. Finally, the small molecule inhibitor of PMVK, PMVKi5, is developed and PMVKi5 inhibits carcinogenesis of liver and colorectal tissues. These findings reveal a non‐canonical function of a key metabolic enzyme PMVK and a novel link between the mevalonate pathway and β‐catenin signaling in carcinogenesis providing a new target for clinical cancer therapy.

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Identification of a cholesterol metabolism-related prognostic signature for multiple myeloma

Zhao,

Qu,

Yang

et al. 2023

Sci Rep

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Multiple myeloma (MM) is a prevalent hematological malignancy that poses significant challenges for treatment. Dysregulated cholesterol metabolism has been linked to tumorigenesis, disease progression, and therapy resistance. However, the correlation between cholesterol metabolism-related genes (CMGs) and the prognosis of MM remains unclear. Univariate Cox regression analysis and LASSO Cox regression analysis were applied to construct an overall survival-related signature based on the Gene Expression Omnibus database. The signature was validated using three external datasets. Enrichment analysis and immune analysis were performed between two risk groups. Furthermore, an optimal nomogram was established for clinical application, and its performance was assessed by the calibration curve and C-index. A total of 6 CMGs were selected to establish the prognostic signature, including ANXA2, CHKA, NSDHL, PMVK, SCAP and SQLE. The prognostic signature demonstrated good prognostic performance and correlated with several important clinical parameters, including number of transplants, International Staging System, albumin, beta2-Microglobulin and lactate dehydrogenase levels. The function analysis and immune analysis revealed that the metabolic pathways and immunologic status were associated with risk score. The nomogram incorporating the signature along with other clinical characteristics was constructed and the discrimination was verified by the calibration curve and C-index. Our findings indicated the potential prognostic connotation of cholesterol metabolism in MM. The development and validation of the prognostic signature is expected to aid in predicting prognosis and guiding precision treatment for MM.

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Phosphomevalonate Kinase Controls β‐Catenin Signaling via the Metabolite 5‐Diphosphomevalonate

Cited by 4 publications

References 50 publications

Genes associated with N6‐methyladenosine regulators provide insight into the prognosis and immune response to renal clear cell carcinoma

Genes associated with N6‐methyladenosine regulators provide insight into the prognosis and immune response to renal clear cell carcinoma

Phosphomevalonate Kinase Controls β‐Catenin Signaling via the Metabolite 5‐Diphosphomevalonate

Identification of a cholesterol metabolism-related prognostic signature for multiple myeloma

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