Resveratrol-downregulated phosphorylated liver kinase B1 is involved in senescence of acute myeloid leukemia stem cells

Background: Emerging evidence closely links Enterovirus 71 (EV71) infection with the generation of reactive oxygen species (ROS). Excess ROS results in apoptosis and exacerbates inflammatory reactions. The Keap1-Nrf2 axis serves as an essential oxidant counteracting pathway. Methods: The present study aimed to elucidate the role of the Keap1-Nrf2 pathway in modulating apoptosis and inflammatory reactions triggered by oxidative stress in Vero and RD cells upon EV71 infection. Results: Elevated ROS production was identified in EV71 infected Vero and RD cells. The percentage of dead cells and expression of inflammation-promoting cytokines were increased in these cells. EV71 infected cells also displayed reinforced Keap1 expression and abrogated Nrf2 expression. Keap1 silencing resulted in the downstream aggregation of the Nrf2 protein and heme oxygenase-1 HO-1. Keap1 silencing repressed ubiquitination and reinforced Nrf2 nuclear trafficking. Furthermore, silencing Keap1 expression repressed ROS production, cell death, and inflammatory reactions in EV71 infected RD and Vero cells. In contrast, silencing of both Keap1 and Nrf2 restored ROS production, cell death, and inflammatory reactions. Nrf2 and Keap1 modulated the stimulation of the Akt sensor and extrinsic as well as intrinsic cell death pathways, resulting in EV71-triggered cell death and inflammatory reactions. Conclusions: EV71 infection can trigger ROS production, cell death, and inflammatory reactions by modulating the Nrf2 and Keap1 levels of infected cells.

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“…Cell death was assessed using Annexin V/propidium iodide (PI) staining and flow cytometry as previously described [17].…”

Section: Analysis Of Cell Deathmentioning

confidence: 99%

RETRACTED ARTICLE: EV71 virus reduces Nrf2 activation to promote production of reactive oxygen species in infected cells

Bai

Zhao

et al. 2020

Gut Pathog

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“…All cells were examined for mycoplasma contamination every year using a mycoplasma staining kit (Beyotime, People's Republic of China). CD38 and CD34 MicroBead kits (Miltenyi, Germany) were used to separate CD34 + CD38 − cells from hCB and bone marrow …”

Section: Methodsmentioning

confidence: 99%

MicroRNA‐34a‐mediated death of acute myeloid leukemia stem cells through apoptosis induction and exosome shedding inhibition via histone deacetylase 2 targeting

et al. 2020

IUBMB Life

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We investigated the role of leukemia stem cells in chemoresistance and recurrence of acute myeloid leukemia. Total RNA was isolated from cells or tissues using TRIzol reagent. Cell viability was assessed with the tetrazolium assay. MicroRNA‐34a (miR‐34a), which acts on cell death regulation pathways, was noticeably downregulated in non‐M3 acute myeloid leukemia stem cells compared with normal hematopoietic stem cells. Furthermore, inhibition of miR‐34a‐mediated suppression in leukemia stem cells was associated with poor clinical outcomes and impaired treatment efficacy in acute myeloid leukemia. Transfection with a miR‐34a mimic triggered leukemia stem cell death and prevented leukemia. Bioinformatics analysis and a dual‐luciferase reporter assay showed that miR‐34a targeted the 3′‐untranslated region of histone deacetylase 2, and the reinforced expression of miR‐34a remarkably stimulated the expression of histone deacetylase 2 in leukemia stem cells. Ectopic miR‐34a expression triggered death of leukemia stem cells via pathways involving the Janus kinase 1‐signal transducer and activator of transcription 2‐p53 axis. Targeting leukemia stem cells to trigger cell death through upregulation of miR‐34a expression could be used to diagnose and treat acute myeloid leukemia.

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“…Apoptotic cells were characterized using Annexin V and propidium iodide (PI) staining with flow cytometry [26]. Apoptotic cells were stained after 48 h of transfection using the Annexin V/PI apoptosis detection kit (KGA-1012, KeyGEN, Nangjing, China).…”

Section: Apoptosis Analysismentioning

confidence: 99%

Long noncoding RNA MALAT1 inhibits the apoptosis and autophagy of hepatocellular carcinoma cell by targeting the microRNA-146a/PI3K/Akt/mTOR axis

Peng

et al. 2020

Cancer Cell Int

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Background: Increased long noncoding RNA (lncRNA) expression is characteristic to hepatocellular carcinoma (HCC) and several other neoplasms. The present study aimed to identify the mechanism underlying modulation of HCC development by the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). Methods: Quantitative real-time polymerase chain reaction was used to determine MALAT1 and microRNA (miR)-146a expression in HCC tissues and cell lines. Western blotting was performed to measure PI3K, Akt, and mTOR levels. Dual-luciferase reporter assay was used to validate the direct targeting and negative regulatory interaction between miR-146a and MALAT1. Cell viability, proliferation, and apoptosis were analyzed using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, colony formation assay, and flow cytometry, respectively; autophagy was detected based on LC3B expression. Results: MALAT1 expression was higher in HCC tissues than in normal tissues. MALAT1 upregulation promoted HCC cell proliferation, whereas MALAT1 downregulation promoted HCC apoptosis and autophagy. Moreover, effects of MALAT1 downregulation on HCC cells were abolished by miR-146a inhibition. miR-146a directly targeted the 3′-untranslated region of PI3K, and PI3K protein level was clearly decreased upon miR-146a mimic transfection. Conclusions: MALAT1 may modulate HCC cell proliferation, apoptosis, and autophagy via sponging miR-146a, which regulates HCC progression.

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Resveratrol-downregulated phosphorylated liver kinase B1 is involved in senescence of acute myeloid leukemia stem cells

Cited by 22 publications

References 25 publications

RETRACTED ARTICLE: EV71 virus reduces Nrf2 activation to promote production of reactive oxygen species in infected cells

RETRACTED ARTICLE: EV71 virus reduces Nrf2 activation to promote production of reactive oxygen species in infected cells

MicroRNA‐34a‐mediated death of acute myeloid leukemia stem cells through apoptosis induction and exosome shedding inhibition via histone deacetylase 2 targeting

Long noncoding RNA MALAT1 inhibits the apoptosis and autophagy of hepatocellular carcinoma cell by targeting the microRNA-146a/PI3K/Akt/mTOR axis

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