Deficiency of VCP-Interacting Membrane Selenoprotein (VIMP) Leads to G1 Cell Cycle Arrest and Cell Death in MIN6 Insulinoma Cells

Men, Lili; Sun, Juan; Ren, Decheng

doi:10.1159/000495865

Cited by 6 publications

(6 citation statements)

References 35 publications

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“…It has been reported that SelS are involved in various cells survival during ER stress and oxidative stress (Lee et al 2015, Men et al 2018a. Consistent with these results, we also found that SelS deficiency induced an augmentation in 3T3-L1 adipocyte apoptosis after induction of differentiation by disruption of the IRE1α-XBP1 pathway, which was associated with an…”

Section: Discussionsupporting

confidence: 91%

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Selenoprotein S regulates adipogenesis through IRE1α-XBP1 pathway

Men

Yao

et al. 2020

Journal of Endocrinology

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The induction of endoplasmic reticulum (ER) stress is associated with adipogenesis, during which the inositol-requiring enzyme 1 alpha (IRE1α)-X-box-binding protein 1 (XBP1) pathway is involved. Selenoprotein S (SelS), which is an ER resident selenoprotein, is involved in ER homeostasis regulation; however, little is known about the role of SelS in regulating adipogenesis. In vivo studies showed that SelS protein levels in white adipose tissue were increased in obese subjects and high-fat diet (HFD)-fed mice. Moreover, we identified that SelS protein levels increased in the early phase of adipogenesis and then decreased in the late phase during adipogenesis. Overexpression of SelS promoted adipogenesis. Conversely, knockdown (KD) of SelS resulted in the inhibition of adipogenesis, which was related to increasing cell death, decreased mitotic clonal expansion, and cell cycle G1 arrest. In vivo studies also showed that ER stress markers (p-IRE1α/IRE1α, XBP1s, and Grp78) were significantly increased with upregulating of SelS expression in subcutaneous and visceral adipose tissues in the obese subjects and HFD-fed mice. Furthermore, in SelS KD cells, the levels of Grp78 were increased and the levels of p-IRE1α/IRE1α were unchanged , but mRNA levels of spliced XBP1 (XBP1s) produced by IRE1α-mediated splicing were decreased, suggesting a role of SelS in the modulation of IRE1α-XBP1 pathway. Moreover, inhibition of adipogenesis by SelS suppression can be rescued by overexpression of XBP1s. Thus, SelS appears to function as a novel regulator of adipogenesis through the IRE1α-XBP1 signaling pathway.

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Section: Discussionsupporting

confidence: 91%

“…Control and SelS KD 3T3-L1 cells after induction for 12, 20, 24, and 28 h were harvested, cell cycle was analysed by flow cytometry as previously reported (Men et al 2018a).…”

Section: Analysis Of Cell Cycle Distributionmentioning

confidence: 99%

Selenoprotein S regulates adipogenesis through IRE1α-XBP1 pathway

Men

Yao

et al. 2020

Journal of Endocrinology

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“…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]. SELENOS was found to be highly expressed in insulinoma cells, and its silencing is able to induce apoptosis by decreasing Bcl-xL in β-cells and to block the cell cycle by downregulating the transcription factor E2F1 and increasing cyclin dependent kinase inhibitor p27 expression [15].…”

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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“…This gene joins the regulation of iron homeostasis and inflammatory responses. Men et al 37 found that VIMP/ SELENOS was associated with cell death and the cell cycle in insulinoma cells. However, there have been few studies on these genes in OV.…”

Section: Discussionmentioning

confidence: 99%

A novel ferroptosis related gene signature is associated with prognosis in patients with ovarian serous cystadenocarcinoma

Chen

et al. 2021

Sci Rep

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Ovarian cancer (OV) is a common type of carcinoma in females. Many studies have reported that ferroptosis is associated with the prognosis of OV patients. However, the mechanism by which this occurs is not well understood. We utilized Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) to identify ferroptosis-related genes in OV. In the present study, we applied Cox regression analysis to select hub genes and used the least absolute shrinkage and selection operator to construct a prognosis prediction model with mRNA expression profiles and clinical data from TCGA. A series of analyses for this signature was performed in TCGA. We then verified the identified signature using International Cancer Genome Consortium (ICGC) data. After a series of analyses, we identified six hub genes (DNAJB6, RB1, VIMP/ SELENOS, STEAP3, BACH1, and ALOX12) that were then used to construct a model using a training data set. The model was then tested using a validation data set and was found to have high sensitivity and specificity. The identified ferroptosis-related hub genes might play a critical role in the mechanism of OV development. The gene signature we identified may be useful for future clinical applications.

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Deficiency of VCP-Interacting Membrane Selenoprotein (VIMP) Leads to G1 Cell Cycle Arrest and Cell Death in MIN6 Insulinoma Cells

Cited by 6 publications

References 35 publications

Selenoprotein S regulates adipogenesis through IRE1α-XBP1 pathway

Selenoprotein S regulates adipogenesis through IRE1α-XBP1 pathway

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

A novel ferroptosis related gene signature is associated with prognosis in patients with ovarian serous cystadenocarcinoma

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