TGF-β induces growth suppression in multiple myeloma MM.1S cells via E2F1

Liu, Xialei; Guo, Hui; Wei, Yuting; Cai, Chaonong; Zhang, Baimeng; Li, Jian

doi:10.3892/ol.2017.6360

Cited by 7 publications

(6 citation statements)

References 27 publications

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“…In MM, tumor cells are confined to the bone marrow microenvironment, and are exposed to high levels of TGF-β secreted from both MM cells and bone marrow stromal cells, leading to further activation of cell growth and survival pathways [ 11 , 12 ]. Notably, it has been demonstrated that upregulation of SMAD1 and ID1 downstream of TGF-β signaling is indicative of activation of this pathway [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

SMAD1 as a biomarker and potential therapeutic target in drug-resistant multiple myeloma

Zhang

Faruq

et al. 2021

Biomark Res

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Background SMAD1, a central mediator in TGF-β signaling, is involved in a broad range of biological activities including cell growth, apoptosis, development and immune response, and is implicated in diverse type of malignancies. Whether SMAD1 plays an important role in multiple myeloma (MM) pathogenesis and can serve as a therapeutic target are largely unknown. Methods Myeloma cell lines and primary MM samples were used. Cell culture, cytotoxicity and apoptosis assay, siRNA transfection, Western blot, RT-PCR, Soft-agar colony formation, and migration assay, Chromatin immunoprecipitation (Chip), animal xenograft model studies and statistical analysis were applied in this study. Results We demonstrate that SMAD1 is highly expressed in myeloma cells of MM patients with advanced stages or relapsed disease, and is associated with significantly shorter progression-free and overall survivals. Mechanistically, we show that SMAD1 is required for TGFβ-mediated proliferation in MM via an ID1/p21/p27 pathway. TGF-β also enhanced TNFα-Induced protein 8 (TNFAIP8) expression and inhibited apoptosis through SMAD1-mediated induction of NF-κB1. Accordingly, depletion of SMAD1 led to downregulation of NF-κB1 and TNFAIP8, resulting in caspase-8-induced apoptosis. In turn, inhibition of NF-κB1 suppressed SMAD1 and ID1 expression uncovering an autoregulatory loop. Dorsomorphin (DM), a SMAD1 inhibitor, exerted a dose-dependent cytotoxic effect on drug-resistant MM cells with minimal cytotoxicity to normal hematopoietic cells, and further synergized with the proteasomal-inhibitor bortezomib to effectively kill drug-resistant MM cells in vitro and in a myeloma xenograft model. Conclusions This study identifies SMAD1 regulation of NF-κB1/TNFAIP8 and ID1-p21/p27 as critical axes of MM drug resistance and provides a potentially new therapeutic strategy to treat drug resistance MM through targeted inhibition of SMAD1.

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Section: Introductionmentioning

confidence: 99%

SMAD1 as a biomarker and potential therapeutic target in drug-resistant multiple myeloma

Zhang

Faruq

et al. 2021

Biomark Res

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“…14 Furthermore, a study has indicated that cell proliferation was suppressed in TGF-b-treated MM.1S cells, which was reversed with anti-E2F1 siRNA treatment. 35 Collectively, this study indicates that suppressed lncRNA LUCAT1 blocked the activation of the TGF-b signaling pathway, thereby suppressing the growth of MM cells. In addition, lncRNA LUCAT1 might be a vital biomarker to assess prognosis in MM survivors.…”

Section: Discussionmentioning

confidence: 63%

“… 14 Furthermore, a study has indicated that cell proliferation was suppressed in TGF-β-treated MM.1S cells, which was reversed with anti-E2F1 siRNA treatment. 35 …”

Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA LUCAT1 Promotes Multiple Myeloma Cell Growth by Regulating the TGF-β Signaling Pathway

Liu

Gao

Peng

et al. 2020

Technol Cancer Res Treat

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Objective: Long noncoding RNAs (lncRNAs) are potential biomarkers for cancers. Nevertheless, the ability of long noncoding RNA lung cancer-associated transcript 1 in patients with multiple myeloma remains unknown. The purpose of this current study was to figure out its function in multiple myeloma. Methods: Firstly, the expression of long noncoding RNA lung cancer-associated transcript 1 in cancer or normal tissues and serum from patients with multiple myeloma and normal donors was detected. Secondly, the expression of long noncoding RNA lung cancer-associated transcript 1 was overexpressed or silenced in U266 and H929 cells, respectively to detect changes of proliferation and apoptosis in multiple myeloma in vitro. Subsequently, the expression of transforming growth factor-β signaling pathway-related proteins was detected by western blot analysis. Finally, the effect of long noncoding RNA lung cancer-associated transcript 1 on the growth of multiple myeloma cells in vivo was evaluated by tumor xenograft in nude mice. Results: Long noncoding RNA lung cancer-associated transcript 1 was increased in cancer tissues and serum of patients with multiple myeloma as well as multiple myeloma cells, which was correlated with dismal prognosis of patients with multiple myeloma. Overexpression of long noncoding RNA lung cancer-associated transcript 1 promoted the activity of U266 and H929 cells, while inhibition of long noncoding RNA lung cancer-associated transcript 1 suppressed the activity of U266 and H929 cells. In addition, long noncoding RNA lung cancer-associated transcript 1 was found to promote activation of the transforming growth factor-β signaling pathway. Furthermore, long noncoding RNA lung cancer-associated transcript 1 knockdown restricted the growth of multiple myeloma cells in vivo. Conclusion: This study suggests that suppression of long noncoding RNA lung cancer-associated transcript 1 inhibits the activation of transforming growth factor-β signaling pathway, thereby inhibiting the growth of multiple myeloma cells.

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“…The E2F family of transcription factors regulate cell function via gene transcription. E2F was reported as a novel fibrotic gene regulating pulmonary fibrosis ( 36 ). The enrichment of single gene GSEA in this study indicated that LPAR1 is significantly enriched in the “E2F target” pathway.…”

Section: Discussionmentioning

confidence: 99%

Identification of inflammation-related biomarkers in keloids

Wang,

Liu

et al. 2024

Front. Immunol.

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BackgroundThe relationship between inflammation-related genes (IRGs) and keloid disease (KD) is currently unclear. The aim of this study was to identify a new set of inflammation-related biomarkers in KD.MethodsGSE145725 and GSE7890 datasets were used in this study. A list of 3026 IRGs was obtained from the Molecular Signatures Database. Differentially expressed inflammation-related genes (DEGs) were obtained by taking the intersection of DEGs between KD and control samples and the list of IRGs. Candidate genes were selected using least absolute shrinkage and selection operator (LASSO) regression analysis. Candidate genes with consistent expression differences between KD and control in both GSE145725 and GSE7890 datasets were screened as biomarkers. An alignment diagram was constructed and validated, and in silico immune infiltration analysis and drug prediction were performed. Finally, RT-qPCR was performed on KD samples to analyze the expression of the identified biomarkers.ResultsA total of 889 DEGs were identified from the GSE145725 dataset, 169 of which were IRGs. Three candidate genes (TRIM32, LPAR1 and FOXF1) were identified by the LASSO regression analysis, and expression validation analysis suggested that FOXF1 and LPAR1 were down-regulated in KD samples and TRIM32 was up-regulated. All three candidate genes had consistent changes in expression in both the GSE145725 and GSE7890 datasets. An alignment diagram was constructed to predict KD. Effector memory CD4 T cells, T follicular helper cell, Myeloid derived suppressor cell, activated dendritic cell, Immature dendritic cell and Monocyte were differentially expressed between the KD and control group. Sixty-seven compounds that may act on FOXF1, 108 compounds that may act on LPAR1 and 56 compounds that may act on TRIM32 were predicted. Finally, RT-qPCR showed that the expression of LPAR1 was significantly lower in KD samples compared to normal samples whereas TRIM32 was significantly higher, while there was no difference in the expression of FOXF1.ConclusionThis study provides a new perspective to study the relationship between IRGs and KD.

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TGF-β induces growth suppression in multiple myeloma MM.1S cells via E2F1

Cited by 7 publications

References 27 publications

SMAD1 as a biomarker and potential therapeutic target in drug-resistant multiple myeloma

SMAD1 as a biomarker and potential therapeutic target in drug-resistant multiple myeloma

Long Noncoding RNA LUCAT1 Promotes Multiple Myeloma Cell Growth by Regulating the TGF-β Signaling Pathway

Identification of inflammation-related biomarkers in keloids

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