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MIR137 Regulates Starvation-Induced Autophagy by Targeting ATG7

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Abstract

Autophagy is a cellular catabolic mechanism in response to stress conditions and has been implicated in the progression and chemoresistance of various cancers. Human microR-137 (MIR137) is involved in neuronal maturation and neurogenesis, while little is known about its role in cancer. In this study, we showed that starvation increased the formation of autophagic marker microtubule-associated protein 1 light chain 3 (LC3) without significant change of MIR137 level in U87 cells. In addition, overexpression of MIR137 decreased LC3 expression and inhibited the degradation of the autophagy receptor sequestosome 1(SQSTM1/p62), while the MIR137 antagomirs showed the opposite effect on these autophagic markers. Moreover, MIR137 overexpression decreased, while its antagomirs increased the expression of autophagy-related 7(ATG7) mRNA and protein. MIR137-mediated inhibition of autophagy was prevented by ATG7. Finally, MIR137 promoted the sensitivity of U87 cells to adriamycin, an anticancer drug. Taken together, our study demonstrated that MIR137 attenuated starvation-induced autophagy by regulating the expression of ATG7.

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Abbreviations

ATG7:

Autophagy-related 7

miRNA:

MicroRNA

LC3:

Microtubule-associated protein 1 light chain 3

MIR137:

Human microRNA-137 and its gene

SQSTM1/P62:

Sequestosome 1

RT-PCR:

Reverse transcriptase-polymerase chain reaction

MTT:

Thiazolyl blue tetrazolium blue

TRIzol:

Trizol Reagent

DMSO:

Dimethyl sulfoxide

GFP:

Green fluorescent protein

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

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Acknowledgments

We would like to thank the Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, for providing useful advice and relevant assistance. The study was supported by the National Key Clinical Specialist Construction Programs of China.

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Correspondence to Gang Huo.

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Zeng, Y., Huo, G., Mo, Y. et al. MIR137 Regulates Starvation-Induced Autophagy by Targeting ATG7. J Mol Neurosci 56, 815–821 (2015). https://doi.org/10.1007/s12031-015-0514-9

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  • DOI: https://doi.org/10.1007/s12031-015-0514-9

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