PARP1-siRNA suppresses human prostate cancer cell growth and progression

Abstract

Poly (ADP-ribose) polymerase (PARP) inhibitors, such as olaparib or rucaparib, have shown treatment efficacy in BRCA1/2-deficient tumors. However, since PARP inhibitors (PARPi) mainly modulate the activation of PARP but not its expression, whether small interfering RNA (siRNA) specific to PARP has the same function as PARPi has not been well defined. In the present study it was demonstrated that PARP1-siRNA could reduce prostate cancer (PCa) cell progression regardless of the BRCA1/2 mutation. PARP1 silencing could significantly inhibit PC3 cell migration and invasion. Additionally, PARP1-siRNA also inhibited the proliferation of PC3 and Du145 cells. After the induction of apoptosis by docetaxel, cleaved-caspase3 of DU145 and C4-2 cells increased significantly in the PARP1-siRNA group. In the xenograft nude mouse model, PARP1-siRNA could suppress xenograft tumor size of PC3 cells and produce a more regular morphology. In vitro and in vivo, PARP1 silencing significantly downregulated vimentin expression and upregulated E-cadherin expression, both of which are epithelial-mesenchymal transition (EMT) markers. It has been revealed that PI3K inhibition could sensitize the effect of PARPi. Notably, PARP1-siRNA could suppress the expression of EGFR and p-GSK3β (Ser9) in PCa cells, which was different from PARPi. Our results indicated that PARP1-siRNA can suppress the growth and invasion capacity of PCa cells, thereby suggesting that PARP1-siRNA, which is different from PARPi, may provide a potential treatment method for PCa.

Identifying the key genes and microRNAs in prostate cancer bone metastasis by bioinformatics analysis

“…Wound healing assays were conducted as described previously [21]. Cell migration was evaluated by measuring the difference in the wound area.…”

Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer

“…This specific adjuvant treatment benefits patients with defective DNA-damage repair such as the BRCA1 and BRCA2 mutations that frequently occur in breast and ovarian cancers [20,21]. Studies involving PARPi for the treatment of PCa are already underway [22,23]. In this context, one strategy for the discovery of new cancer biomarkers and/or potential therapeutic targets is to integrate genomic data from genetically engineered mouse models (GEMMs) and human cancer patients [24,25].…”

Biguanides in combination with olaparib limits tumorigenesis of drug‐resistant ovarian cancer cells through inhibition of Snail

“…Moreover, PARP‐1 was shown to be prometastatic in melanoma in vitro and in vivo through vimentin‐induced E‐cadherin down regulation, Snail activation and consequently increased cell motility and migration . In addition, PARP‐1 silencing in prostate cancer promoted E‐cadherin expression and suppressed GSK‐3β phosphorylation, a crucial step in EMT signaling . This indicates that PARP silencing or maybe even PARP inhibition may have the efficacy of blocking EMT and attenuating metastasis.…”

“…29 In addition, PARP-1 silencing in prostate cancer promoted E-cadherin expression and suppressed GSK-3β phosphorylation, a crucial step in EMT signaling. 30 This indicates that PARP silencing or maybe even PARP inhibition may have the efficacy of blocking EMT and attenuating metastasis.…”