TRAF6 Silencing Attenuates Multiple Myeloma Cell Adhesion to Bone Marrow Stromal Cells

Morgan, Jonathan J.; McAvera, Roisin; Crawford, Lisa

doi:10.3390/ijms20030702

Cited by 12 publications

(8 citation statements)

References 34 publications

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“…NF-κB is an inactive heterodimer composed of p50 and p65 subunits interacting with a member of the inhibitory IκB family in resting cells (Bai et al, 2016). Upon stimulation by activating signals, the IKK complex phosphorylates IκBα, promoting its degradation and freeing NFκB p50/p65 to translocate to the nucleus and initiate transcription (Wang et al, 2017; Morgan et al, 2019). In our study, mTOR deficiency suppressed NF-κB activation followed by decreased levels of the NLRP3 inflammasome.…”

Section: Discussionmentioning

confidence: 99%

Rapamycin Attenuates High Glucose-Induced Inflammation Through Modulation of mTOR/NF-κB Pathways in Macrophages

et al. 2019

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Background: The NLRP3 inflammasome is one of the key contributors to impaired wound healing in diabetes. In this study, we assessed the role of rapamycin on high glucose-induced inflammation in THP-1-derived macrophages and investigated the underlying signaling mechanisms.Methods: THP-1-derived macrophages were treated with high glucose to induce NLRP3 inflammasome activation. The cells were pretreated with rapamycin, BAY 11-7082, or PDTC before exposure to HG. mTOR, NF-κB, and NLRP3 inflammasome expression were measured by western blotting.Results: We found that rapamycin reduced NLRP3 inflammasome activation in macrophages. Rapamycin reduced NLRP3 inflammasome activation by inhibiting mTOR phosphorylation and NF-κB activation. Moreover, mTOR siRNA inhibited NF-κB activation, leading to the suppression of NLRP3 inflammasome activation.Conclusion: Rapamycin can ameliorate high glucose-induced NLRP3 inflammasome activation by attenuating the mTOR/NF-κB signaling pathway in macrophages. Rapamycin may act as a possible therapeutic option for high glucose-induced inflammatory response in impaired wound healing in the future.

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Section: Discussionmentioning

confidence: 99%

Rapamycin Attenuates High Glucose-Induced Inflammation Through Modulation of mTOR/NF-κB Pathways in Macrophages

et al. 2019

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“…Therefore, TRAF6 has become a potential therapeutic target for multiple tumors, such as multiple myeloma, liver cancer, and melanoma [42][43][44]. The adhesion of multiple myeloma cells to bone marrow stromal cells leads to activation of tumor-promoting signaling pathways, while TRAF6 promotes adhesion through NF-κBinduced adhesion factors [45]. Although previous study showed that TRAF6 does not affect NF-κB pathway in cancer cells under normal condition [46], Zhu et al found that TRAF6 promotes colorectal cancer cells (SW48 and HCT116) proliferation and migration through NF-κB nuclear translocation [47].…”

Section: Traf6 and Nf-κb Pathwaymentioning

confidence: 99%

The relationship between TRAF6 and tumors

Liu

Tang

et al. 2020

Cancer Cell Int

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Tumor necrosis factor receptor (TNFR)-related factors (TRAFs) are important linker molecules in the tumor necrosis factor superfamily (TNFSF) and the Toll-like/interleukin-1 receptor (TLR/ILR) superfamily. There are seven members: TRAF1-TRAF7, among those members, tumor necrosis factor receptor-associated factor 6 (TRAF6) is upregulated in various tumors, which has been related to tumorigenesis and development. With the in-depth study of the relationship between TRAF6 and different types of tumors, TRAF6 has oncogenic characteristics involved in tumorigenesis, tumor development, invasion, and metastasis through various signaling pathways, therefore, targeting TRAF6 has provided a novel strategy for tumor treatment. This review summarizes and analyzes the role of TRAF6 in tumorigenesis and tumor development in combination with the current research on TRAF6 and tumors.

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“…Fang J. et al [9] showed that the absence of Traf6 reduces the self-renewal ability of hematopoietic stem cells, and results in premature death and hematological defects. A recent study [23] reported that activating the NFκB pathway is the key to the pathogenesis of MM and TRAF6 has been previously found to act as an important mediator in NFκB activation. Through rescue experiments, we discovered that the effect of TRAF6 on cells was opposite to that of miR-361-3p on the MM cells.…”

Section: Discussionmentioning

confidence: 99%

The Effect of miR-361-3p Targeting TRAF6 on Apoptosis of Multiple Myeloma Cells

Fan

Yang

2021

J. Microbiol. Biotechnol.

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microRNA-361-3p (miR-361-3p) is involved in the carcinogenesis of oral cancer and pancreatic catheter adenocarcinoma, and has anti-carcinogenic effects on non-small cell lung cancer (NSCLC). However, its effect on multiple myeloma (MM) is less reported. Here, we found that upregulating the expression of miR-361-3p inhibited MM cell viability and promoted MM apoptosis. We measured expressions of tumor necrosis factor receptor-associated factor 6 (TRAF6) and miR-361-3p in MM cells and detected the viability, colony formation rate, and apoptosis of MM cells. In addition, we measured expressions of apoptosis-related genes Bcl-2, Bax, and Cleaved caspase-3 (C caspase-3). The binding site between miR-361-3p and TRAF6 was predicted by TargetScan. Our results showed that miR-361-3p was low expressed in the plasma of MM patients and cell lines, while its overexpression inhibited viability and colony formation of MM cells and increased the cell apoptosis. Furthermore, TRAF6, which was predicted to be a target gene of miR-361-3p, was highexpressed in the plasma of patients and cell lines with MM. Rescue experiments demonstrated that the effect of TRAF6 on MM cells was opposite to that of miR-361-3p. Upregulation of miR-361-3p induced apoptosis and inhibited the proliferation of MM cells through targeting TRAF6, suggesting that miR-361-3p might be a potential target for MM therapy.

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TRAF6 Silencing Attenuates Multiple Myeloma Cell Adhesion to Bone Marrow Stromal Cells

Cited by 12 publications

References 34 publications

Rapamycin Attenuates High Glucose-Induced Inflammation Through Modulation of mTOR/NF-κB Pathways in Macrophages

Rapamycin Attenuates High Glucose-Induced Inflammation Through Modulation of mTOR/NF-κB Pathways in Macrophages

The relationship between TRAF6 and tumors

The Effect of miR-361-3p Targeting TRAF6 on Apoptosis of Multiple Myeloma Cells

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