NF-κB promotes the stem-like properties of leukemia cells by activation of LIN28B

Zhou, Jianbiao; Chooi, Jing-Yuan; Ching, Ying Qing; Quah, Jessie Yiying; Toh, Sabrina Hui-Min; Ng, Yan Ling; Tan, Tuan Zea; Chng, Wee‐Joo

doi:10.4252/wjsc.v10.i4.34

Cited by 11 publications

(7 citation statements)

References 29 publications

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“…The pro-inflammatory transcription factor NF-κB, has been found to be aberrantly activated in LSCs but is not expressed in normal human CD34+ progenitor cells [16][17][18]. NF-κB is known to mediate chemoresistance by upregulation of anti-apoptotic genes, which enable cells to increase proliferation and evade apoptosis [19][20][21]. Targeting NF-κB may be selective for LSCs and/or sensitize LSCs to chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Targeting PI3K/Akt/mTOR in AML: Rationale and Clinical Evidence

Darici

Alkhaldi

Horne

et al. 2020

JCM

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Acute myeloid leukemia (AML) is a highly heterogeneous hematopoietic malignancy characterized by excessive proliferation and accumulation of immature myeloid blasts in the bone marrow. AML has a very poor 5-year survival rate of just 16% in the UK; hence, more efficacious, tolerable, and targeted therapy is required. Persistent leukemia stem cell (LSC) populations underlie patient relapse and development of resistance to therapy. Identification of critical oncogenic signaling pathways in AML LSC may provide new avenues for novel therapeutic strategies. The phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathway, is often hyperactivated in AML, required to sustain the oncogenic potential of LSCs. Growing evidence suggests that targeting key components of this pathway may represent an effective treatment to kill AML LSCs. Despite this, accruing significant body of scientific knowledge, PI3K/Akt/mTOR inhibitors have not translated into clinical practice. In this article, we review the laboratory-based evidence of the critical role of PI3K/Akt/mTOR pathway in AML, and outcomes from current clinical studies using PI3K/Akt/mTOR inhibitors. Based on these results, we discuss the putative mechanisms of resistance to PI3K/Akt/mTOR inhibition, offering rationale for potential candidate combination therapies incorporating PI3K/Akt/mTOR inhibitors for precision medicine in AML.

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Section: Introductionmentioning

confidence: 99%

Targeting PI3K/Akt/mTOR in AML: Rationale and Clinical Evidence

Darici

Alkhaldi

Horne

et al. 2020

JCM

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“…Lin28B has been verified to be a target gene of NF-κB 19, 36. Therefore, we further explored whether curcumin could downregulate the expression of Lin28B through NF-κB.…”

Section: Resultsmentioning

confidence: 99%

Lin28b is involved in curcumin-reversed paclitaxel chemoresistance and associated with poor prognosis in hepatocellular carcinoma

Tian¹,

Shangguan²,

Zhou³

et al. 2019

J. Cancer

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Chemoresistance remains a big challenge in hepatocellular carcinoma (HCC) treatment. Several studies indicated that RNA-binding protein Lin28B serves an oncogenic role in HCC, but its activity in HCC chemotherapy has never been assessed. In this study, we found that overexpression of Lin28B significantly increased the paclitaxel chemoresistance in two different HCC cells lines while silencing Lin28B reduced the chemoresistance in paclitaxel-resistance HCC cells. Curcumin, a natural anti-cancer agent, increased the sensitivity of HCC cells to paclitaxel through inhibiting NF-κB stimulated Lin28B expression both in vitro and in vivo. Furthermore, by analyzing TCGA (The Cancer Genome Atlas) LIHC (liver hepatocellular carcinoma) and GSE14520 databases, we found that Lin28B was highly upregulated in HCC tissue compared with that in normal tissue and associated with α‑fetoprotein levels, and that patients with Lin28B higher expression had a significant shorter overall survival time than those with Lin28B lower expression. Our data reveal that Lin28B may serve as a predictive biomarker and a treatment target to reverse HCC chemotherapy resistance in future clinical practice.

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“…Zhou and collaborators demonstrated that NF-κB fosters stem-like properties (i.e., self-renewal capacity) of AML cells via LIN28B activation. Accordingly, NF-κB inhibition reduces LIN28B expression and cell survival as well as LSCs’ self-renewal in vitro, suggesting that inhibition of NF-κB could be a potential opportunity to kill AML cells and LSCs in order to counteract cancer resistance and disease relapse [ 29 ].…”

Section: Nf-κb Pathway In Aml Pathogenesismentioning

confidence: 99%

NF-κB: A Druggable Target in Acute Myeloid Leukemia

Francesco

Verzella

Capece

et al. 2022

Cancers

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Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy that relies on highly heterogeneous cytogenetic alterations. Although in the last few years new agents have been developed for AML treatment, the overall survival prospects for AML patients are still gloomy and new therapeutic options are still urgently needed. Constitutive NF-κB activation has been reported in around 40% of AML patients, where it sustains AML cell survival and chemoresistance. Given the central role of NF-κB in AML, targeting the NF-κB pathway represents an attractive strategy to treat AML. This review focuses on current knowledge of NF-κB’s roles in AML pathogenesis and summarizes the main therapeutic approaches used to treat NF-κB-driven AML.

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NF-κB promotes the stem-like properties of leukemia cells by activation of LIN28B

Cited by 11 publications

References 29 publications

Targeting PI3K/Akt/mTOR in AML: Rationale and Clinical Evidence

Targeting PI3K/Akt/mTOR in AML: Rationale and Clinical Evidence

Lin28b is involved in curcumin-reversed paclitaxel chemoresistance and associated with poor prognosis in hepatocellular carcinoma

NF-κB: A Druggable Target in Acute Myeloid Leukemia

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