Mechanism of mitochondrial protease LONP1 in the biological behavior of prostate cancer / 肿瘤
Tumor
;
(12): 171-185, 2023.
Artículo
en Chino
| WPRIM
| ID: wpr-1030273
ABSTRACT
Objective:
To explore the mechanism of Ion peptidase 1,mitochondrial(LONP1)in the progression of castration-resistant prostate cancer(CRPC).Methods:
The expression levels of LONP1,N-Myc downstream-regulated gene 1(NDRG1)and androgen receptor(AR)proteins in benign prostatic hyperplasia cell line BPH-1,androgen-dependent human prostate cancer cell line LNCaP and castration-resistant prostate cancer(CRPC)cell line PC3 were examined by Western blotting.Recombinant vector carrying full-length LONP1 gene was delivered into LNCaP cells via lentiviral infection to establish stable LONP1-overexpressing(OE-LONP1)cell line,and LNCaP cells transfected with empty vector was used as the corresponding negative control(OE-NC).shRNA specifically targeting LONP1 gene(shLONP1)was delivered into PC3 cells to establish stable LONP1-silencing cell line,and PC3 cells transfected with empty shRNA vector(shNC)was used as the negative control.The effect of LONP1-overexpression and silencing on cell proliferation and invasion was analyzed by CCK-8 assay,colony formation assay and Transwell invasion assay in OE-LONP1 and shLONP1 cell lines.The effect of LONP1 on the AR/DNRG1 signaling axis was analyzed by co-immunoprecipitation assay and chromatin immunoprecipitation assay.The effect of NDRG1-silencing on the proliferation and invasion of shLONP1-expressing PC3 cells was evaluated by CCk-8 assay and Transwell assay.Tumor xenograft model was established by subcutaneously inoculating shLONP1-expressing PC3 cells and the negative control cells(PC3-shNC cells)into BALB/c nude mice.The mice were treated with DMSO or AR antagonist enzalutamide(ENZ).Then,the expression level of Ki-67 in tumor tissues was examined by immunohistochemical staining,and the cell apoptosis in tumor tissues was evaluated by TUNEL assay.Results:
Compared with BPH-1 cells,LNCaP cells had lower(P<0.05)while PC3 cells had higher(P<0.05)expression level of LONP1 protein.The expression of AR and NDRG1 were inhibited in LNCaP cells when LONP1 was overexpressed(P<0.05),whereas the expression of AR and NDRG1 were increased in PC3 cells when LONP1 was silenced(P<0.05).The proliferation and invasion of LNCaP cells were promoted when LONP1 was overexpressed(P<0.05),whereas the proliferation and invasion of PC3 cells were suppressed when LONP1 was knocked-down(P<0.05).LONP1 can directly bind with AR to recognize the androgen response element(ARE)of NDRG1,which further inhibits the AR/NRDG1 signaling pathway to promote the progression of prostate cancer.The treatment of xenograft tumors in mouse models showed that both LONP1-silencing and ENZ application could inhibit tumor growth,and the best inhibitory effect was observed in mice treated with LONP1-silencing in combination with ENZ.The results of immunohistochemical staining and TUNEL assay indicated that the tumor tissues in the shLONP1+ENZ group had lower level of Ki-67 expression and higher level of cell apoptosis(P<0.001).Conclusion:
LONP1 is highly expressed in CRPC cell line PC3,and promotes prostate cancer progression by inhibiting AR/NDRG1 signaling transduction.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Idioma:
Chino
Revista:
Tumor
Año:
2023
Tipo del documento:
Artículo
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