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GOLPH3 promotes glioma progression via facilitating JAK2–STAT3 pathway activation

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Introduction

Our recent work reported that GOLPH3 promotes glioma progression via inhibiting endocytosis and degradation of EGFR. The current study aimed to explore the potential regulating mechanism of GOLPH3 on JAK2–STAT3 signaling, a downstream effector of EGFR, in glioma progression.

Methods

The expression of JAK2, STAT3 and GOLPH3 in glioma tissues was detected by western blotting, tissue microarray and immunohistochemistry. The U251 and U87 cells with GOLPH3 down-regulation or over-expression were generated by lentivirus system. The effects of GOLPH3 on the activity of JAK2 and STAT3 were detected by western blotting and reverse transcription polymerase chain reaction. Co-immunoprecipitation was used to detect the association of GOLPH3 with JAK2 and STAT3. Cell proliferation was detected by CCK8 and EdU assay.

Results

The level of JAK2, STAT3 and GOLPH3 were significantly up-regulated and exhibited pairwise correlation in human glioma tissues. The level of p-JAK2 and p-STAT3, as well as the mRNA and protein levels of cyclin D1 and c-myc, two target genes of STAT3, decreased after GOLPH3 down-regulation, while they increased after GOLPH3 over-expression both in U251 and U87 cells. Interestingly, GOLPH3, JAK2 and STAT3 existed in the same protein complex and GOLPH3 affected the interaction of JAK2 and STAT3. Importantly, down-regulation of STAT3 partially abolished cell proliferation induced by GOLPH3 over-expression.

Conclusions

GOLPH3 may act as a scaffold protein to regulate JAK2–STAT3 interaction and then its activation, which therefore mediates the effect of GOLPH3 on cell proliferation.

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Acknowledgements

This study was funded by National Natural Science Foundation of China (Grant Nos: 81672489; 81472345); Six Major Talent Summit of Jiangsu Province (Grant No: 2014-WSW-039). We thank professor Chunmei Zhu in School of International Education of Xuzhou Medical University for English writing assistance.

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Author notes

  1. Yanhua Qi

    Present address: Emergency Center of the Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, Jiangsu, People’s Republic of China

  2. Shishuang Wu and Jiale Fu have contributed equally to this work.

Authors and Affiliations

  1. The Graduate School, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, People’s Republic of China

    Shishuang Wu, Jiale Fu, Yu Dong, Qinghao Yi, Weibing Wang & Yanhua Qi

  2. Institute of Nervous System Diseases, Xuzhou Medical University, 84 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People’s Republic of China

    Dong Lu, Rutong Yu & Xiuping Zhou

  3. Brain Hospital, Affiliated Hospital of Xuzhou Medical University, 99 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People’s Republic of China

    Dong Lu, Rutong Yu & Xiuping Zhou

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  1. Shishuang Wu
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Correspondence to Rutong Yu or Xiuping Zhou.

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Wu, S., Fu, J., Dong, Y. et al. GOLPH3 promotes glioma progression via facilitating JAK2–STAT3 pathway activation. J Neurooncol 139, 269–279 (2018). https://doi.org/10.1007/s11060-018-2884-7

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