Metformin inhibits IL-6 signaling by decreasing IL-6R expression on multiple myeloma cells

Mishra, Akshay; Dingli, David

doi:10.1038/s41375-019-0470-4

Cited by 62 publications

(55 citation statements)

References 43 publications

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“…IL-6 signaling plays a crucial role in the pathogenesis of MM, and small molecule inhibitors targeting IL-6 signaling are highly effective at preventing MM cell growth. 8 We speculate that tocilizumab might also have potential benefit for MM as an immunotherapy in the future. This case is the first to prove that tocilizumab is effective in the treatment of COVID-19 in MM with obvious clinical recovery; however, randomized controlled trials are needed to determine the safety and efficacy of tocilizumab.…”

Section: Resultsmentioning

confidence: 90%

First case of COVID-19 in a patient with multiple myeloma successfully treated with tocilizumab

et al. 2020

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Section: Resultsmentioning

confidence: 90%

First case of COVID-19 in a patient with multiple myeloma successfully treated with tocilizumab

et al. 2020

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“…IL-6 is critical for the growth and survival of malignant PCs, and several factors and mechanisms can increase IL-6 levels ( 21 ). However, IL-6 must bind to its receptor to elicit its effects as IL-6R transduces the IL-6 signal ( 5 ). The molecular mechanisms regulating IL-6R expression have not yet been fully elucidated ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

“…IL-6 exerts its biological activities by binding to its receptor (IL-6R). The levels of both IL-6 and IL-6R are upregulated in patients with MM ( 5 ). IL-6R leads to activation of the JAK-STAT signaling pathway to regulate the proliferation and apoptosis of myeloma cells ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

miR‑451a suppression of IL‑6R can inhibit proliferation and increase apoptosis through the JAK2/STAT3 pathway in multiple myeloma

Zhong

Jin

et al. 2020

Oncol Lett

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The IL-6R/JAK2/STAT3 pathway mediated by interleukin-6 (IL-6) plays an important role in the occurrence and development of multiple myeloma (MM), which is associated with decreased microRNA-451a. However, the biological function of microRNA-451a in MM remains unclear. The bone marrow (BM) of patients with MM was sampled, and the plasma cells were enriched. BM miR-451a, IL-6 and IL-6R levels and Ki-67 expression intensity were evaluated using reverse transcription-quantitative PCR, ELISA and flow cytometry, respectively. U266 cell proliferation, viability and apoptosis were measured using BrdU, CCK-8 and Annexin V/propidium iodide assays, respectively. Total and phospo-(p-)JAK2 and p-STAT3 levels were measured by western blotting. Dual-luciferase reporter assays were performed to validate the predicted target binding sites. miR-451a expression was low in patients with MM and was associated with the Revised International Staging System (R-ISS) stage. IL-6 concentrations were significantly higher in patients with MM than in normal controls and were inversely associated with miR-451a levels (r=−0.96, P<0.0001). IL-6R levels were positively correlated with the R-ISS stage. miR-451a was downregulated, and IL-6R was upregulated in myeloma cell lines. Treatment with an miR-451a mimic inhibited viability and induced apoptosis in U266 cells. p-JAK2 and p-STAT3 levels were significantly lower in mimic-treated U266 cells than in control cells. Thus, miR-451a was shown to regulate myeloma cell proliferation and apoptosis via the IL-6R/JAK2/STAT3 pathway and may be used to predict patient prognosis.

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“…31 IL-6 signaling plays a role in the pathogenesis of multiple myeloma (MM), and disruption of IL-6 signaling is known to inhibit MM cell growth. 32 IL-6 is among the key components of the inflammatory cascade responsible for host defense against several…”

Section: Dovepressmentioning

confidence: 99%

<p>Repurposing Anti-Cancer Drugs for COVID-19 Treatment</p>

Borcherding

Jethava

Vikas

2020

DDDT

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Metformin inhibits IL-6 signaling by decreasing IL-6R expression on multiple myeloma cells

Cited by 62 publications

References 43 publications

First case of COVID-19 in a patient with multiple myeloma successfully treated with tocilizumab

First case of COVID-19 in a patient with multiple myeloma successfully treated with tocilizumab

miR‑451a suppression of IL‑6R can inhibit proliferation and increase apoptosis through the JAK2/STAT3 pathway in multiple myeloma

<p>Repurposing Anti-Cancer Drugs for COVID-19 Treatment</p>

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