miR‐34a inhibits the apoptosis of MDSCs by suppressing the expression of N‐myc

Chen, Si; Huang, Anfei; Chen, Huo; Yang, Yi; Xia, Fei; Jin, Liping; Zhang, Jinping

doi:10.1038/icb.2016.11

Cited by 14 publications

(8 citation statements)

References 47 publications

(72 reference statements)

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“…MiR-34a was able to induce MDSC expansion both in chimera and transgenic mice. Detailed study found that overexpression of miR-34a could inhibit MDSC apoptosis by suppressing the expression of N-myc but without affecting MDSC proliferation [ 72 ]. This study implied that down-regulation of miR-34a could reduce the number of infiltrated MDSCs in tumor by inducing apoptosis.…”

Section: Post-transcriptional Regulation Of Mdscs With Mirnasmentioning

confidence: 99%

Epigenetics in myeloid derived suppressor cells: a sheathed sword towards cancer

et al. 2016

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Myeloid-derived suppressor cells (MDSCs), a heterogeneous population of cells composed of progenitors and precursors to myeloid cells, are deemed to participate in the development of tumor-favoring immunosuppressive microenvironment. Thus, the regulatory strategies targeting MDSCs' expansion, differentiation, accumulation and function could possibly be effective “weapons” in anti-tumor immunotherapies. Epigenetic mechanisms, which involve DNA modification, covalent histone modification and RNA interference, result in the heritable down-regulation or silencing of gene expression without a change in DNA sequences. Epigenetic modification of MDSC's functional plasticity leads to the remodeling of its characteristics, therefore reframing the microenvironment towards countering tumor growth and metastasis. This review summarized the pertinent findings on the DNA methylation, covalent histone modification, microRNAs and small interfering RNAs targeting MDSC in cancer genesis, progression and metastasis. The potentials as well as possible obstacles in translating into anti-cancer therapeutics were also discussed.

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Section: Post-transcriptional Regulation Of Mdscs With Mirnasmentioning

confidence: 99%

Epigenetics in myeloid derived suppressor cells: a sheathed sword towards cancer

et al. 2016

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“…MDSCs are often elevated in infectious and inflammatory pathological conditions. By directly targeting N-Myc, miR-34a may induce the expansion of MDSCs in the bone marrow and spleen as a result of reduced apoptosis (Chen S. et al, 2016). Overexpressed miR-34a changes the cytokine expression profile in MDSCs with increased TNF-α and iNOS, thus partially attenuating lung tumor growth (Chen S. et al, 2016).…”

Section: Myeloid-derived Suppressor Cellsmentioning

confidence: 99%

MicroRNA-34a: Potent Tumor Suppressor, Cancer Stem Cell Inhibitor, and Potential Anticancer Therapeutic

Wang

Liu

et al. 2021

Front. Cell Dev. Biol.

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Overwhelming evidence indicates that virtually all treatment-naive tumors contain a subpopulation of cancer cells that possess some stem cell traits and properties and are operationally defined as cancer cell stem cells (CSCs). CSCs manifest inherent heterogeneity in that they may exist in an epithelial and proliferative state or a mesenchymal non-proliferative and invasive state. Spontaneous tumor progression, therapeutic treatments, and (epi)genetic mutations may also induce plasticity in non-CSCs and reprogram them into stem-like cancer cells. Intrinsic cancer cell heterogeneity and induced cancer cell plasticity, constantly and dynamically, generate a pool of CSC subpopulations with varying levels of epigenomic stability and stemness. Despite the dynamic and transient nature of CSCs, they play fundamental roles in mediating therapy resistance and tumor relapse. It is now clear that the stemness of CSCs is coordinately regulated by genetic factors and epigenetic mechanisms. Here, in this perspective, we first provide a brief updated overview of CSCs. We then focus on microRNA-34a (miR-34a), a tumor-suppressive microRNA (miRNA) devoid in many CSCs and advanced tumors. Being a member of the miR-34 family, miR-34a was identified as a p53 target in 2007. It is a bona fide tumor suppressor, and its expression is dysregulated and downregulated in various human cancers. By targeting stemness factors such as NOTCH, MYC, BCL-2, and CD44, miR-34a epigenetically and negatively regulates the functional properties of CSCs. We shall briefly discuss potential reasons behind the failure of the first-in-class clinical trial of MRX34, a liposomal miR-34a mimic. Finally, we offer several clinical settings where miR-34a can potentially be deployed to therapeutically target CSCs and advanced, therapy-resistant, and p53-mutant tumors in order to overcome therapy resistance and curb tumor relapse.

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“…The over-expression of miR-34a results in an increase of MDSCs due to a reduction of MDSCs apoptosis. The proto-oncogene N-myc which is a transcription factor that has a role in activities, including cell growth, differentiation, and apoptosis, is a target of miR-34a in MDSCs ( 88 ). As a result, restoring miR-34a expression contemporarily to stopping TGF-β signaling might offer a promising molecular treatment in concert with MDSC inhibition in cancer.…”

Section: Micro Rnasmentioning

confidence: 99%

MicroRNAs and lncRNAs—A New Layer of Myeloid-Derived Suppressor Cells Regulation

et al. 2020

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Myeloid-derived suppressor cells (MDSCs) constitute an important component in regulating immune responses in several abnormal physiological conditions such as cancer. Recently, novel regulatory tumor MDSC biology modulating mechanisms, including differentiation, expansion and function, were defined. There is growing evidence that miRNAs and long non-coding RNAs (lncRNA) are involved in modulating transcriptional factors to become complex regulatory networks that regulate the MDSCs in the tumor microenvironment. It is possible that aberrant expression of miRNAs and lncRNA contributes to MDSC biological characteristics under pathophysiological conditions. This review provides an overview on miRNAs and lncRNAs epiregulation of MDSCs development and immunosuppressive functions in cancer.

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miR‐34a inhibits the apoptosis of MDSCs by suppressing the expression of N‐myc

Cited by 14 publications

References 47 publications

Epigenetics in myeloid derived suppressor cells: a sheathed sword towards cancer

Epigenetics in myeloid derived suppressor cells: a sheathed sword towards cancer

MicroRNA-34a: Potent Tumor Suppressor, Cancer Stem Cell Inhibitor, and Potential Anticancer Therapeutic

MicroRNAs and lncRNAs—A New Layer of Myeloid-Derived Suppressor Cells Regulation

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