Dual-specificity phosphatase 26 inhibits proliferation, migration, and invasion of prostate cancer via the TAK1-JNK/p38 signaling pathway

Abstract

Abstract As the most frequently identified malignant tumor of the male genitourinary system, prostate cancer (PCa) is threatening the health of millions of people worldwide because of its malignant, easy-to-transfer, and complicated complications. Moreover, the complex pathological mechanism of prostate cancer has not been fully elaborated and needs to be further explored. Here, we found that the expression of DUSP26, a deubiquitylation enzyme, is dramatically suppressed, and a positive connection of its expression with PCa prognosis was also observed. In vitro, overexpression of DUSP26 significantly inhibited the proliferative, migrative, and invasive capacities of PC3 cell, DUSP26 silencing presented opposite results. Further tumor formation experiments in subcutaneous nude mice demonstrated that DUSP26 overexpression could significantly suppress PC3 growth in vivo. Moreover, it also suggested that the DUSP26 overexpression negatively connected to key tumorigenesis signaling pathways through analysis of RNA-Seq. Mechanically, DUSP26 significantly inhibited MAPK signaling pathway activation, and further experiments displayed that DUSP26 could impair TAK1, p38, and JNK phosphorylation. Interestingly, treatment with the TAK1 inhibitor attenuated the effect of DUSP26 on PC3 cells. Together, these results suggested that DUSP26 may serve as a novel therapeutic target for PC3 cell type PCa by inhibiting the TAK1-JNK/p38 signaling.