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Cell Stress and Chaperones

, Volume 24, Issue 1, pp 105–113 | Cite as

MiR-4465 directly targets PTEN to inhibit AKT/mTOR pathway–mediated autophagy

  • Zhouteng Tao
  • Chenxi Feng
  • Chenmei Mao
  • Jin Ren
  • Yusi Tai
  • Huijie Guo
  • Mei Pu
  • Yang Zhou
  • Guanghui Wang
  • Mei WangEmail author
Original Paper
  • 129 Downloads

Abstract

Autophagy plays an important role in maintaining cell function. Abnormal autophagy leads to cell dysfunction and is associated with many diseases such as tumors, immunodeficiency diseases, lysosomal storage disorders, and neurodegenerative diseases. Autophagy is precisely regulated, and PTEN plays an important role in regulating autophagy. As noncoding small RNAs, miRNAs play an important role in the fine regulation of cellular processes. However, the mechanism of the miRNA regulation of PTEN-related autophagy has not been fully elucidated. In this study, our results showed that miR-4465 significantly inhibited the expression of PTEN, upregulated phosphorylated AKT, and thereby inhibited autophagy by activating mTOR in HEK293, HeLa, and SH-SY5Y cells. Further studies indicated that miR-4465 reduced PTEN mRNA levels through posttranscriptional regulation via directly targeting the 3′-UTR. Our novel findings provide useful hints for the comprehensive elucidation of the molecular mechanism of miRNA-regulated PTEN-related autophagy and may also provide some new insights for the exploration of miRNAs in the treatment of PTEN-related diseases.

Keywords

Autophagy miR-4465 PTEN mTOR 

Abbreviations

PTEN

Phosphatase and tensin homolog deleted on chromosome ten

mTOR

Mammalian target of Rapamycin

MAPK

Mitogen-activated protein kinase

Baf A1

Bafilomycin A1

Notes

Acknowledgements

We thank Professor Guanghui Wang and Jin Ren for their kind help with revising the manuscript.

Formatting of funding sources

This study was supported by the National Youthful Science Foundation of China (No. 81701261), the National Natural Science Foundation of China (No. 81501181), and the Natural Science Foundation of Jiangsu Province (BK20150290).

Authors’ contributions

All the authors contributed significantly to the study. M.W. and Z.T. designed the study, conducted the experiments, and wrote the manuscript. The immunoblotting, immunofluorescence, cell transfection, and statistical analysis were performed by Z.T., C.F., and C.M. The cell culture and viability detection were performed by Y.T. and H.G. The plasmids were constructed by M.P. and Y.Z., and G.W. and J.R. revised the manuscript. All the authors are in agreement with the content of the manuscript for publication.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

12192_2018_946_MOESM1_ESM.docx (518 kb)
ESM 1 (DOCX 517 kb)

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Copyright information

© Cell Stress Society International 2018

Authors and Affiliations

  1. 1.Department of PharmacyChildren’s Hospital of Soochow UniversitySuzhouChina
  2. 2.Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug ResearchShanghai Institute of Materia Medica, Chinese Academy of SciencesShanghaiChina
  3. 3.School of Life Science and TechnologyShanghaiTech UniversityShanghaiChina
  4. 4.Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical SciencesSoochow UniversitySuzhouChina

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