Adipose tissue hyperplasia with enhanced adipocyte-derived stem cell activity in Tc1(C8orf4)-deleted mice

Jang, Ha-Young; Kim, Min-Sung; Lee, So‐Young; Kim, Jung‐Tae; Woo, Dong‐Cheol; Kim, Kyung Won; Song, Kyuyoung; Lee, Inchul

doi:10.1038/srep35884

Cited by 18 publications

(17 citation statements)

References 38 publications

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“…The present study observed that the expression of TC1, β-catenin, and DNMT1 were correlated with each other, indicating that these three proteins might promote the activity of the Wnt signaling pathway in a synergistic manner. Recent studies revealed that TC1 plays a role in the regulation of stem cells, such as hematopoietic stem cells [ 16 ], adipocyte-derived stem cells [ 29 ], and liver cancer stem cells [ 22 ] via the Wnt/β-catenin signaling pathway or Notch signaling pathway. Therefore, TC1 may participate in tumorigenesis and the transformation of cancer stem cells, which require further studies.…”

Section: Discussionmentioning

confidence: 99%

Thyroid cancer 1 (C8orf4) shows high expression, no mutation and reduced methylation level in lung cancers, and its expression correlates with β-catenin and DNMT1 expression and poor prognosis

et al. 2017

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Thyroid cancer 1 (TC1, C8orf4) plays important roles in tumors. The aim of this study was to examine the protein expression levels, methylation status, and mutational status of TC1 (C8orf4) in lung cancers, and investigate the correlation between TC1, other members of the Wnt signaling pathway, and lung cancer. TC1 expression levels were assessed via immunohistochemical staining in 179 cases of lung cancer. β-catenin, TCF4, Axin, Disabled-2, Chibby, and DNA methyltransferase-1 (DNMT1) expressions were also examined. Bisulfite sequencing PCR analysis was used to examine the methylation status of the C8orf4 locus, while PCR analysis and direct sequencing were used to determine its mutational status. We found high TC1 expression correlated with poor differentiation, advanced TNM stage, lymphatic metastasis, and poor prognosis in lung cancer patients. TC1 expression also correlated with β-catenin and DNMT1 expressions. No mutations in C8orf4 were detected. However, methylation levels of C8orf4 in lung cancers were lower than in corresponding normal lung tissues. In conclusion, high TC1 expression is implicated in lung cancer progression and correlates with poor prognosis in lung cancer. Reduced methylation levels might be responsible for the elevated TC1 expression levels. TC1, β-catenin, and DNMT1 can synergistically activate Wnt/β-catenin signaling in lung cancers.

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Section: Discussionmentioning

confidence: 99%

Thyroid cancer 1 (C8orf4) shows high expression, no mutation and reduced methylation level in lung cancers, and its expression correlates with β-catenin and DNMT1 expression and poor prognosis

et al. 2017

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“…By using Targetscan, candidate downstream transcripts of miR‐30a were analyzed and predicted; of these predicted candidates, the potential role of C8orf4 (Tc1) in adipogenesis has been previously reported. Tc1 −/− ADSC proliferated more actively; moreover, CEBP‐α and PPARγ are upregulated robustly in Tc1 −/− ADSCs upon induction for adipogenesis (Jang et al, ). In the present study, miR‐30a directly bound to the 3′‐UTR of C8orf4 to negatively regulate the mRNA expression and the protein levels of C8orf4.…”

Section: Discussionmentioning

confidence: 99%

H19/miR‐30a/C8orf4 axis modulates the adipogenic differentiation process in human adipose tissue‐derived mesenchymal stem cells

Yang

et al. 2019

Journal Cellular Physiology

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The adipogenic differentiation of adipose tissue-derived mesenchymal stem cells (ADSCs) is a critical issue in many obesity-related disorders. Cytidine-cytidine-adenosineadenosine-thymidine (CCAAT) enhancer binding protein α (CEBP-α) and peroxisome proliferator-activated receptor-γ are two important lipogenic and adipogenic transcription factors and markers in adipogenic differentiation. Noncoding RNAs participate in adipogenic differentiation. The long noncoding RNA (lncRNA) H19 is related to multiple cellular differentiation, including adipogenic differentiation; however, its function and precise molecular mechanism in human ADSCs (hADSCs) adipogenic differentiation are unclear. microRNAs that were differentially expressed in adipogenic differentiation and could be targeted by H19 were screened and selected; the regulation and interaction between H19 and miR-30a were verified. The interaction between miR-30a and predicted downstream target C8orf4 was validated. The dynamic effects of H19 and miR-30a on C8orf4 messenger RNA (mRNA) expression and protein and adipogenic differentiation were evaluated. miR-30a negatively regulated H19 with each other through direct binding. As predicted by TargetScan and verified using luciferase reporter gene assays, miR-30a directly bound to the 3′-untranslated region of C8orf4 to inhibit its expression; H19 knockdown suppressed while miR-30a inhibition promoted the mRNA expression and the protein levels of C8orf4 and adipogenic differentiation; the effect of H19 knockdown could be partially reversed by miR-30a inhibition. The lncRNA H19 serves as a competing endogenous RNA (ceRNA) for miR-30a to augment miR-30a downstream target C8orf4, therefore modulating adipogenic differentiation in hADSCs.From the perspective of lncRNA-miRNA-mRNA regulation, we provided a novel regulatory mechanism of hADSCs adipogenic differentiation. K E Y W O R D S adipogenic differentiation, C8orf4, human adipose tissue-derived mesenchymal stem cells, lncRNA H19, miR-30a

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“…KO studies have also identified Tc1 as a factor that inhibits the expandability of adipose tissue by suppressing adipocyte hyperplasia, as Tc1 KO mice had increased adiposity, but with small hyperplastic adipocytes, reduced circulating lipids and improved glucose tolerance in vivo. ASCs from these animals correspondingly exhibited increased proliferation and enhanced adipocytic differentiation in ex vivo culture (Jang et al, ). Given that Tc1 is upregulated by inflammatory cytokines in other cell types (Y. Kim et al, ), this protein may form part of the mechanism perpetuating pathological adipocyte hypertrophy and adipose tissue inflammation observed during obesity (Heinonen et al, ; Vieira et al, ).…”

Section: Overview Of Recently Published Work In Ascsmentioning

confidence: 99%

Adipocyte biology: It is time to upgrade to a new model

Gijsen

2018

Journal Cellular Physiology

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Globally, the obesity pandemic is profoundly affecting quality of life and economic productivity, but efforts to address this, especially on a pharmacological level, have generally proven unsuccessful to date, serving as a stark demonstration that our understanding of adipocyte biology and pathophysiology is incomplete. To deliver better insight into adipocyte function and obesity, we need improved adipocyte models with a high degree of fidelity in representing the in vivo state and with a diverse range of experimental applications. Adipocyte cell lines, especially 3T3-L1 cells, have been used extensively over many years, but these are limited in terms of relevance and versatility. In this review, I propose that primary adipose-derived stromal/stem cells (ASCs) present a superior model with which to study adipocyte biology ex vivo. In particular, ASCs afford us the opportunity to study adipocytes from different, functionally distinct, adipose depots and to investigate, by means of in vivo/ex vivo studies, the effects of many different physiological and pathophysiological factors, such as age, body weight, hormonal status, diet and nutraceuticals, as well as disease and pharmacological treatments, on the biology of adipocytes and their precursors. This study will give an overview of the characteristics of ASCs and published studies utilizing ASCs, to highlight the areas where our knowledge is lacking. More comprehensive studies in primary ASCs will contribute to an improved understanding of adipose tissue, in healthy and dysfunctional states, which will enhance our efforts to more successfully manage and treat obesity.

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Adipose tissue hyperplasia with enhanced adipocyte-derived stem cell activity in Tc1(C8orf4)-deleted mice

Cited by 18 publications

References 38 publications

Thyroid cancer 1 (C8orf4) shows high expression, no mutation and reduced methylation level in lung cancers, and its expression correlates with β-catenin and DNMT1 expression and poor prognosis

Thyroid cancer 1 (C8orf4) shows high expression, no mutation and reduced methylation level in lung cancers, and its expression correlates with β-catenin and DNMT1 expression and poor prognosis

H19/miR‐30a/C8orf4 axis modulates the adipogenic differentiation process in human adipose tissue‐derived mesenchymal stem cells

Adipocyte biology: It is time to upgrade to a new model

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