Selenoprotein M stimulates the proliferative and metastatic capacities of renal cell carcinoma through activating the PI3K/AKT/mTOR pathway

Jiang, Hao; Shi, Qianqian; Ge, Liyuan; Zhuang, Qianfeng; Xue, Dong; Xu, Haiyan; He, Xiaozhou

doi:10.1002/cam4.2403

Cited by 22 publications

(17 citation statements)

References 32 publications

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“…Previous studies have proved the several classical signaling mechanisms were involved in promoting ccRCC, such as VHL/HIF1α [40], PI3K/Akt/mTOR [41], HGF/MET [42], MAPK [43], and Wnt/β-Catenin [44], etc. TRPV1 expression was discovered to be negatively correlated with expression of the key proteins in those pathways and positively correlated to cancer inhibiting genes, p53 and VHL.…”

Section: Discussionmentioning

confidence: 99%

TRPV1 acts as a Tumor Suppressor and is associated with Immune Cell Infiltration in Clear Cell Renal Cell Carcinoma: evidence from integrated analysis

Zheng¹,

Dou²,

Song³

et al. 2020

J. Cancer

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Differential expression of TRPV1 has been detected in many cancer types, including clear cell renal cell carcinoma (ccRCC). However, the clinical significance of TRPV1 expression profile in ccRCC has not been comprehensively elucidated. In this study, TRPV1 expression in ccRCC and other cancer types was analyzed based on data from the GEO and Oncomine databases. Immunohistochemical (IHC) staining was performed for further validation in human ccRCC tissue chips. Survival and correlation analyses of TRPV1 were conducted using Kaplan-Meier Plotter (KM-Plotter) and the Tumor IMmune Estimation Resource (TIMER) database. TRPV1 exhibited a low expression profile in 2 GEO datasets (GSE6344, GSE36895) and 4 Oncomine datasets (Gumz, Lenburg, Beroukhim 1 and Beroukhim 2), as also confirmed by IHC staining. Survival analysis indicated that high enrichment of TRPV1 significantly predicted a better overall survival (OS) and disease-free survival (DFS) of 1, 3, 5 and 10 years in ccRCC patients. TIMER analysis showed that TRPV1 copy number alterations (CNA) were closely related to immune cell infiltration. The detailed results indicated that TRPV1 expression was positively correlated with the infiltration level of CD4+ T cells, but negatively correlated with B cells, macrophages, and dendritic cells infiltration. In addition, TRPV1 might also be inversely related to abundance of the regulatory T cells (Treg) and the M2 subset of macrophages. Finally, we found that TRPV1 expression was tightly associated with several key molecules of the classical pathways in ccRCC, such as VHL, TP53, HIF1A, MTOR, MAPK1, MET, CTNNB1, etc. Our research work suggests that TRPV1 is a novel tumor suppressor and prognosis marker for ccRCC and is of great value for further exploration.

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Section: Discussionmentioning

confidence: 99%

TRPV1 acts as a Tumor Suppressor and is associated with Immune Cell Infiltration in Clear Cell Renal Cell Carcinoma: evidence from integrated analysis

Zheng¹,

Dou²,

Song³

et al. 2020

J. Cancer

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“…SelK and SelS were reported to be involved in degradation of misfolded proteins in endoplasmic reticulum [29]. It has been revealed recently that SelM activates the PI3K/Akt/mTOR pathway and mediate expression of matrix metallopeptidases 2 and 9 in renal cell carcinoma [44]. However, the function of some selenoproteins such as SelO, SelI is not elucidated yet [33,34].…”

Section: Selenium Status and Its Biological Importance: Selenium In Tmentioning

confidence: 99%

Selenium Anticancer Properties and Impact on Cellular Redox Status

et al. 2020

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(1) Background: In this review, we provide information published in recent years on the chemical forms, main biological functions and especially on antioxidant and prooxidant activities of selenium. The main focus is put on the impact of selenoproteins on maintaining cellular redox balance and anticancerogenic function. Moreover, we summarize data on chemotherapeutic application of redox active selenium compounds. (2) Methods: In the first section, main aspects of metabolism and redox activity of selenium compounds is reviewed. The second outlines multiple biological functions, asserted when selenium is incorporated into the structure of selenoproteins. The final section focuses on anticancer activity of selenium and chemotherapeutic application of redox active selenium compounds as well. (3) Results: optimal dietary level of selenium ensures its proper antioxidant and anticancer activity. We pay special attention to antioxidant activities of selenium compounds, especially selenoproteins, and their importance in antioxidant defence. It is worth noting, that data on selenium anticancer properties is still contraversive. Moreover, selenium compounds as chemotherapeutic agents usually are used at supranutritional doses. (4) Conclusions: Selenium play a vital role for many organism systems due to its incorporation into selenoproteins structure. Selenium possesses antioxidant activity at optimal doses, while at supranutritional doses, it displays prooxidant activity. Redox active selenium compounds can be used for cancer treatment; recently special attention is put to selenium containing nanoparticles.

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“…Several additional reports also demonstrated the role of specific selenoproteins in other cancer types. High levels of SELENOM were associated with poor prognosis of renal cell carcinoma (RCC), and preclinical evidence demonstrated that SELENOM silencing was able to block cancer proliferation, invasion, migration, and tumorigenesis, via PI3K/AKt/mTOR pathway inhibition and reduced metalloproteinases (MMP) 2 and 9 expression [13]. SELENOK was found to have a crucial role in the proliferation and activation of immune cells and the promotion of calcium flux that induces melanoma progression [14].…”

Section: Introductionmentioning

confidence: 99%

Integrated Analysis to Study the Relationship between Tumor-Associated Selenoproteins: Focus on Prostate Cancer

Capone

Polo

Sorice

et al. 2020

IJMS

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Selenoproteins are proteins that contain selenium within selenocysteine residues. To date, twenty-five mammalian selenoproteins have been identified; however, the functions of nearly half of these selenoproteins are unknown. Although alterations in selenoprotein expression and function have been suggested to play a role in cancer development and progression, few detailed studies have been carried out in this field. Network analyses and data mining of publicly available datasets on gene expression levels in different cancers, and the correlations with patient outcome, represent important tools to study the correlation between selenoproteins and other proteins present in the human interactome, and to determine whether altered selenoprotein expression is cancer type-specific, and/or correlated with cancer patient prognosis. Therefore, in the present study, we used bioinformatics approaches to (i) build up the network of interactions between twenty-five selenoproteins and identify the most inter-correlated proteins/genes, which are named HUB nodes; and (ii) analyze the correlation between selenoprotein gene expression and patient outcome in ten solid tumors. Then, considering the need to confirm by experimental approaches the correlations suggested by the bioinformatics analyses, we decided to evaluate the gene expression levels of the twenty-five selenoproteins and six HUB nodes in androgen receptor-positive (22RV1 and LNCaP) and androgen receptor–negative (DU145 and PC3) cell lines, compared to human nontransformed, and differentiated, prostate epithelial cells (EPN) by RT-qPCR analysis. This analysis confirmed that the combined evaluation of some selenoproteins and HUB nodes could have prognostic value and may improve patient outcome predictions.

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Selenoprotein M stimulates the proliferative and metastatic capacities of renal cell carcinoma through activating the PI3K/AKT/mTOR pathway

Cited by 22 publications

References 32 publications

TRPV1 acts as a Tumor Suppressor and is associated with Immune Cell Infiltration in Clear Cell Renal Cell Carcinoma: evidence from integrated analysis

TRPV1 acts as a Tumor Suppressor and is associated with Immune Cell Infiltration in Clear Cell Renal Cell Carcinoma: evidence from integrated analysis

Selenium Anticancer Properties and Impact on Cellular Redox Status

Integrated Analysis to Study the Relationship between Tumor-Associated Selenoproteins: Focus on Prostate Cancer

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