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Emerging Role of MicroRNAs in mTOR Signaling

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Abstract

Mechanistic target of rapamycin (mTOR) is a conserved serine/threonine kinase that plays a critical role in the control of cellular growth and metabolism. Hyperactivation of mTOR pathway is common in human cancers, driving uncontrolled proliferation. MicroRNA (miRNA) is a class of short noncoding RNAs that regulate the expression of a wide variety of genes. Deregulation of miRNAs is a hallmark of cancer. Recent studies have revealed interplays between miRNAs and the mTOR pathway during cancer development. Such interactions appear to provide a fine-tuning of various cellular functions and contribute qualitatively to the behavior of cancer. Here we provide an overview of current knowledge regarding the reciprocal relationship between miRNAs and mTOR pathway: regulation of mTOR signaling by miRNAs and control of miRNA biogenesis by mTOR. Further research in this area may prove important for the diagnosis and therapy of human cancer.

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Abbreviations

AMPK:

Adenosine 5′-monophosphate-activated protein kinase

BDNF:

Brain-derived neurotrophic factor

DDIT4:

DNA damage-inducible transcript 4

4E-BP1:

eIF4E-binding protein 1

IGF-1/IGF1R:

Insulin-like growth factor 1/insulin-like growth factor 1 receptor

IKKβ:

IkB kinaseβ

IRS:

Insulin receptor substrate

LKB1:

Liver kinase B1

MiRNA:

microRNA

mTOR:

Mechanistic/mammalian target of rapamycin

mTORC1/2:

mTOR complex 1/2

p70S6K:

70 kDa ribosomal protein S6 kinase

PDCD4:

Programmed cell death 4

PI3K:

Phosphoinositide 3-kinase

PRAS40:

Proline-rich AKT substrate 40 kDa

PTEN:

Phosphatase and tensin homolog

Rheb:

Ras homology enriched in brain

Stat3:

Signal transducer and activator of transcription 3

TSC1/2:

Tuberous sclerosis 1/2

VEGF:

Vascular Endothelial Growth Factor

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Acknowledgements

Related work in authors’ laboratories was supported by NIH R01 Grants CA123391, CA166575, and CA173519, the National Natural Science Foundation of China 81672354, 81372600, 81572440, and Shanghai Pujiang Program 15PJ1404900.

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Authors and Affiliations

  1. Oncology Department, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201999, China

    Yanjie Zhang & Bo Huang

  2. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China

    Hui-Yun Wang & X. F. Steven Zheng

  3. Rutgers Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ, 08854, USA

    Hui-Yun Wang & X. F. Steven Zheng

  4. Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, 195 Little Albany Street, New Brunswick, NJ, 08903, USA

    Hui-Yun Wang, Augustus Chang & X. F. Steven Zheng

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  1. Yanjie Zhang
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  2. Bo Huang
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  3. Hui-Yun Wang
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  4. Augustus Chang
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  5. X. F. Steven Zheng
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Correspondence to Yanjie Zhang or X. F. Steven Zheng.

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Zhang, Y., Huang, B., Wang, HY. et al. Emerging Role of MicroRNAs in mTOR Signaling. Cell. Mol. Life Sci. 74, 2613–2625 (2017). https://doi.org/10.1007/s00018-017-2485-1

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  • DOI: https://doi.org/10.1007/s00018-017-2485-1

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