Cancer Letters

Cancer Letters

Volume 427, 28 July 2018, Pages 38-48
Cancer Letters

Original Articles
Protein arginine methyltransferase 5 promotes lung cancer metastasis via the epigenetic regulation of miR-99 family/FGFR3 signaling

https://doi.org/10.1016/j.canlet.2018.04.019Get rights and content
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Highlights

  • PRMT5 promoted metastasis, in vitro and in vivo, by epigenetic regulation of miR-99 family and consequent FGFR3 pathways.

  • PRMT5 repressed the transcription of miR-99 family by symmetrical dimethylation of histone H4R3.

  • The miR-99 family loss increased the transcription of FGFR3 to activate Erk1/2 and Akt.

  • PRMT5 expression was positively related to FGFR3 in lung cancer, and indicated poor prognosis of patients.

Abstract

Protein arginine methyltransferase 5 (PRMT5) functions as a tumor initiator to regulate several cancer progressions, such as proliferation and apoptosis, by catalyzing the symmetrical dimethylation (me2s) of arginine residues within targeted molecules. However, the exact role of PRMT5-mediated metastasis in lung cancer is not fully understood. Here, we illustrated its potential effects in lung cancer metastasis in vivo and vitro. PRMT5 was frequently overexpressed in lung tumors, and its expression was positively related to tumor stages, lymphatic metastasis and poor outcome. In this model, PRMT5 repressed the transcription of the miR-99 family by symmetrical dimethylation of histone H4R3, which increased FGFR3 expression and in turn activated Erk1/2 and Akt, leading to cell growth and metastasis in lung cancer. Furthermore, loss of PRMT5 exerted anti-metastasis effects on lung cancer progression by blocking histone-modification of miR-99 family. Overall, this study provides new insights into the PRMT5/miR-99 family/FGFR3 axis in regulating lung cancer progression and identifies PRMT5 as a promising prognostic biomarker and therapeutic target.

Keywords

Lung cancer
Tumor progression
PRMT5
miR-99 family
H4R3me2s
FGFR3

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1

These authors contributed equally to this work.