Shushang Chen, Mingfang Weng, Ronghui Lin, Junjie Wei, Lingfeng Zhu, Zhenghua Ju, Zhitao Lin, Bin Zhan, Ram A Pathak, Rashid K Sayyid, Rong Ge
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引用次数: 0
Abstract
Background: New medications are needed to improve outcomes of castration-resistant prostate cancer (CRPC). Psoralen has been reported to have anti-cancer properties for various tumors, but there are limited reports about psoralen treatment in prostate cancer (PCa). This study aimed to investigate the effect of psoralen on PC3 cells and to investigate potential underlying mechanisms of action.
Methods: The effect of psoralen on the proliferation and cell cycle progression of PC3 cells was determined using Cell Counting Kit-8 (CCK-8) test and flow cytometry, respectively. The differential gene profiles in PC3 cells treated with psoralen were determined with microarray analyses. The effect of psoralen on long non-coding RNA (lncRNA) ENST00000510619 expression in PC3 cells was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The effect of psoralen and transfection of small interfering lnc-RNA (si-lncRNA) ENST00000510619 on cell viability, invasion ability, and migratory activity of PC3 cells were evaluated using the CCK-8 test, transwell assay, and wound healing, respectively.
Results: Psoralen significantly inhibited PC3 cells in a concentration- and time-dependent manner and caused G1 phase and G2/M phase cycle arrests. When screened with a fold change (FC) of ≥2 and a P value of <0.05, 1,716 lncRNAs and 1,160 messenger RNAs (mRNAs) were significantly up-regulated, whereas 3,269 lncRNAs and 3,263 mRNAs were significantly down-regulated in PC3 cells after psoralen treatment. Among the differentially down-regulated lncRNAs in which the signal of the probe showed significant differences compared to the background, lncRNA ENST00000510619 had the highest FC. The expression of lncRNA ENST00000510619 was shown to be down-regulated by psoralen in a concentration-dependent manner. CCK-8 assay, wound healing, and transwell assay showed that both psoralen and si-lncRNA ENST00000510619 transfection significantly inhibited the activity, invasion, and migration of PC3 cells (P<0.01 for all).
Conclusions: Psoralen was confirmed to inhibit proliferation and block the cell cycle in PC3 cells in this in vitro study. The molecular mechanism involves multiple differentially expressed lncRNAs and mRNAs and is related to the down-regulation of lncRNA ENST000000510619 expression. This study provides the experimental basis for the development of psoralen as a novel anti-CRPC drug and for the consideration of lncRNA ENST00000510619 as a potential clinical target for CRPC.
期刊介绍：
ranslational Andrology and Urology (Print ISSN 2223-4683; Online ISSN 2223-4691; Transl Androl Urol; TAU) is an open access, peer-reviewed, bi-monthly journal (quarterly published from Mar.2012 - Dec. 2014). The main focus of the journal is to describe new findings in the field of translational research of Andrology and Urology, provides current and practical information on basic research and clinical investigations of Andrology and Urology. Specific areas of interest include, but not limited to, molecular study, pathology, biology and technical advances related to andrology and urology. Topics cover range from evaluation, prevention, diagnosis, therapy, prognosis, rehabilitation and future challenges to urology and andrology. Contributions pertinent to urology and andrology are also included from related fields such as public health, basic sciences, education, sociology, and nursing.
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