Prmt6-flox Mouse

Prmt6, short for Protein arginine methyltransferase 6, is a type I PRMT. It is involved in epigenetic regulation of gene expression through methylating histone or non-histone proteins, and also participates in processes like alternative splicing, DNA repair, cell proliferation, senescence, and cell signaling [7].

PRMT6 has been shown to play significant roles in multiple diseases. In breast cancer, it positively regulates tumor metastasis by asymmetrically di-methylating STAT3 at arginine 729, which is essential for STAT3's membrane localization, interaction with JAK2, Y705 phosphorylation, and cancer cell metastasis. The PRMT6 inhibitor, EPZ020411, can curtail breast cancer metastasis in vivo and in vitro [1].

In glioblastoma, PRMT6 activity is required for the proliferation, stem-like properties, and tumorigenicity of glioblastoma stem cells. Disrupting the CK2-PRMT6-RCC1 signaling axis leads to mitosis defects, and EPZ020411 suppresses RCC1 arginine methylation and improves radiotherapy cytotoxicity against GSC brain tumor xenografts [2].

In lung cancer, PRMT6 is highly expressed and regulates cell metabolism, tumorigenicity, and cisplatin response by increasing the activity of 6PGD and ENO1. Targeting PRMT6 blocks metabolic pathways and enhances cisplatin's anti-tumor effects [3].

In acute myeloid leukemia, PRMT6 is crucial for maintaining leukemia stem cells. Genetic deletion or pharmacological inhibition of PRMT6 impairs AML development and LSC function [4].

In diabetic nephropathy, PRMT6 down-regulation participates in kidney dysfunction and renal cell death via ferroptosis modulation. The PRMT6/STAT1/ACSL1 axis may be a new therapeutic target [5].

In neuropathic pain, PRMT6 deficiency or inhibition alleviates pain by decreasing glycolysis and inflammation in microglia [6].

In glioblastoma, silencing PRMT6 inhibits cell proliferation and induces cell cycle arrest, while overexpressing it has the opposite effect. PRMT6 promotes the ubiquitinated degradation of CDKN1B and cell proliferation via CDC20, and the PRMT6 inhibitor can attenuate GBM cell proliferation [8].

In osteoporosis, PRMT6 deficiency or inhibitor impedes osteoclast differentiation and alleviates bone loss by reversing the metabolic shift from fatty acid oxidation to glycolysis [9].

In glioblastoma, PRMT6 promotes migration, invasion, and EMT via the PRMT6-YTHDF2-Wnt-β-Catenin axis [10].

In conclusion, Prmt6 is vital in epigenetic regulation and various biological processes. Studies using gene knockout or inhibitor-based models have revealed its key roles in cancer, diabetic nephropathy, neuropathic pain, and osteoporosis. These findings provide potential therapeutic targets for these diseases, highlighting the importance of Prmt6 in understanding disease mechanisms and developing treatments.