biostudies-literatureUnknown34(1)Hu BCurrent treatments for prostate cancer (PC) inevitably lead to the development of resistance to androgen deprivation therapy, resulting in the emergence of castration-resistant prostate cancer (CRPC), which is currently considered incurable. In this study, we discovered that the loss of phosphatase and tensin homolog (PTEN) function, in combination with elevated poly(ADP-ribose) polymerase 1 (PARP1) expression, significantly shortens the survival of PC patients. Motivated by this finding, we developed an RNA-based therapeutic agent consisting of PARP1-targeting small interfering RNA (siRNA) (siPARP1) and PTEN-expressing mRNA (mPTEN), which were co-encapsulated in an ionizable lipid nanoparticle, named mPsiP@miLAND. Both siPARP1 and mPTEN were shown to individually attenuate tumor cell growMolecular therapy. Oncology201133https://www.ebi.ac.uk/biostudies/studies/S-EPMC12905993biostudies-literatureSuppression of PARP1 enhances PTEN mRNA therapy in castration-resistant prostate cancer by glycolysis disruption.PMC12905993Yang HYang JFan YZhang JWu PYang MLiu QHu BZhu CTang LHuang YZheng LKong SfalseSuppression of PARP1 enhances PTEN mRNA therapy in castration-resistant prostate cancer by glycolysis disruption.Current treatments for prostate cancer (PC) inevitably lead to the development of resistance to androgen deprivation therapy, resulting in the emergence of castration-resistant prostate cancer (CRPC), which is currently considered incurable. In this study, we discovered that the loss of phosphatase and tensin homolog (PTEN) function, in combination with elevated poly(ADP-ribose) polymerase 1 (PARP1) expression, significantly shortens the survival of PC patients. Motivated by this finding, we developed an RNA-based therapeutic agent consisting of PARP1-targeting small interfering RNA (siRNA) (siPARP1) and PTEN-expressing mRNA (mPTEN), which were co-encapsulated in an ionizable lipid nanoparticle, named mPsiP@miLAND. Both siPARP1 and mPTEN were shown to individually attenuate tumor cell grow2026-01-01T00:00:00Z2026 Mar2026-07-15T21:21:18.918Z2026-07-09T10:15:18.191ZS-EPMC129059934169663110.1016/j.omton.2026.201133