Treatment and resistance mechanisms in castration-resistant prostate cancer: new implications for clinical decision making?

Norz, Valentina; Rausch, Steffen

doi:10.1080/14737140.2021.1843430

Cited by 4 publications

(1 citation statement)

References 170 publications

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“…Currently, continuous in-depth studies have developed various new drugs for CRPC. Nonetheless, this poses a major clinical challenge, including the selection of tailored for individual patients, the optimal combination of these new effective drugs, and an exploration of the mechanisms underlying acquired resistance ( Norz & Rausch, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Niraparib restrains prostate cancer cell proliferation and metastasis and tumor growth in mice by regulating the lncRNA MEG3/miR-181-5p/GATA6 pathway

Cheng,

Sun,

Zhao

et al. 2023

PeerJ

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Background Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi), have gained approval for treating patients with castration-resistant prostate cancer (CRPC). Maternally expressed gene 3 (MEG3), a long non-coding RNA (lncRNA), plays a role in inhibiting tumorigenesis through regulating DNA repair genes. This study aimed to investigate the association between the anti-prostate cancer (PCa) effect of niraparib, a representative PARPi, and MEG3 expression, as well as explore the downstream pathway involved. Methods The levels of MEG3, miR-181-5p, GATA binding protein 6 (GATA6) in clinical samples from PCa patients were accessed by RT-qPCR. PC3 cells were treated with niraparib, and the expression of MEG3, miR-181-5p, GATA6 expression was tested. PC3 cell proliferation, migration, and invasion were tested by CCK-8, wound healing, and Transwell assays, respectively. The bindings between miR-181-5p and MEG3/GATA6 were determined by dual-luciferase reporter gene assay. Furthermore, rescue experiments were conducted to investigate the underlying mechanism of MEG3/miR-181-5p/GATA6 axis in PCa progression. Additionally, mice were injected with PC3 cells transfected with sh-MEG3 and treated with niraparib, and the xenograft tumor growth was observed. Results MEG3 and GATA6 were upregulated and miR-181-5p was downregulated in PCa patients. Niraparib treatment substantially upregulated MEG3 and GATA6, and downregulated miR-181-5p expression in PCa cells. Niraparib effectively restrained PC3 cell proliferation, migration, and invasion. MiR-181-5p targeted to MEG3, and the inhibitory effects of MEG3 overexpression on PC3 cell proliferation and metastasis were abrogated by miR-181-5p overexpression. Moreover, GATA6 was identified as a target of miR-181-5p, and GATA6 silencing abolished the inhibitory effects of miR-181-5p inhibition on PC3 cell proliferation and metastasis. Besides, MEG3 silencing could abrogate niraparib-mediated tumor growth inhibition in mice. Conclusions Niraparib restrains prostate cancer cell proliferation and metastasis and tumor growth in mice by regulating the lncRNA MEG3/miR-181-5p/GATA6 pathway.

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Section: Introductionmentioning

confidence: 99%