Title : NPRL2 enhances autophagy and the resistance to Everolimus in castration-resistant prostate cancer.

Pub. Date : 2019 Jan

PMID : 30178500






11 Functional Relationships(s)
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1 NPRL2 enhances autophagy and the resistance to Everolimus in castration-resistant prostate cancer. Everolimus NPR2 like, GATOR1 complex subunit Mus musculus
2 However, the role of NPRL2 in regulating the resistance to Everolimus (EVS), an inhibitor of the mTOR, in castration-resistant prostate cancer (CRPC) is still unclear. Everolimus NPR2 like, GATOR1 complex subunit Mus musculus
3 Therefore, in present study, we evaluated the role of NPRL2 and its potential resistance to EVS in CRPC. Everolimus NPR2 like, GATOR1 complex subunit Mus musculus
4 METHODS: NPRL2 expression levels in prostate tissues, including benign prostate hyperplasia (BPH) tissues, primary prostate cancer (PCa) tissues, CRPC tissues, and several PCa cell lines (LNCaP, PC3, and enzalutamide-resistant LNCaP, named LNPER) were be evaluated by immunohistochemistry, RT-PCR, and Western blot. enzalutamide NPR2 like, GATOR1 complex subunit Mus musculus
5 Lastly, relationship between NPRL2 expression level and the efficacy of EVS were evaluated in mice tumor xenograft models. Everolimus NPR2 like, GATOR1 complex subunit Mus musculus
6 NPRL2 over-expression promoted the proliferation, resistance to EVS, and NPRL2 silencing inhibited proliferation, enhanced sensitivity to EVS in PC3 and LNPER cells. Everolimus NPR2 like, GATOR1 complex subunit Mus musculus
7 Moreover, NPRL2-silencing increased the activity of mTOR signaling, and the autophagy attenuation induced by NPRL2-silencing in EVS-treated CRPC cells was associated with the increase of apoptosis. Everolimus NPR2 like, GATOR1 complex subunit Mus musculus
8 Moreover, NPRL2-silencing increased the activity of mTOR signaling, and the autophagy attenuation induced by NPRL2-silencing in EVS-treated CRPC cells was associated with the increase of apoptosis. Everolimus NPR2 like, GATOR1 complex subunit Mus musculus
9 In addition, the growth prevention of NPRL2-silencing LNPER tumors in mice induced by EVS-treatment was associated with the autophagy attenuation and apoptosis increase. Everolimus NPR2 like, GATOR1 complex subunit Mus musculus
10 The high levels of NPRL2 expression in CRPC promote resistance to EVS by enhancing autophagy. Everolimus NPR2 like, GATOR1 complex subunit Mus musculus
11 NPRL2 may be a new therapeutic target for intervention of CRPC and a biomarker for predicting resistance to EVS in CRPC. Everolimus NPR2 like, GATOR1 complex subunit Mus musculus