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前列腺癌相关基因的转录本保留在前列腺上皮细胞的核内。

Transcripts of the Prostate Cancer-Associated Gene Are Retained in the Nuclei of Prostatic Epithelial Cells.

机构信息

Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 25020 Turku, Finland.

FICAN West Cancer Center, University of Turku and Turku University Hospital, Kiinamyllynkatu 10, 25020 Turku, Finland.

出版信息

Int J Mol Sci. 2023 Jan 5;24(2):1052. doi: 10.3390/ijms24021052.

Abstract

Prostate cancer affects millions of men globally. The prostate cancer-associated gene is downregulated in advanced prostate cancer, whereas benign tissue and low-grade cancer display varying expression levels. In this study, we assess the spatial correlation between mRNA and protein using fluorescent in situ hybridization and immunohistochemistry for the detection of mRNA and protein in parallel sections of tissue microarrays prepared from radical prostatectomy samples. We show that mRNA and protein expression correlate in prostate tissue. Furthermore, we show that mRNA is enriched in the nuclei of the luminal cells at 89% in benign ducts and low-grade cancer, and at 78% in high-grade cancer. The nuclear enrichment of mRNA was validated in prostate cancer cell lines 22Rv1 and MDA PCa 2b using droplet digital polymerase chain reaction (ddPCR) on RNA isolated from nuclear and cytoplasmic fractions of the cells. The nuclear enrichment of mRNA was compared to the nuclearly-enriched lncRNA , confirming the surprisingly high nuclear retention of mRNA. has been suggested to be used as a diagnostic marker and a target for immunotherapy, but a full comprehension of its role in prostate cancer progression is currently lacking. Our results contribute to a better understanding of the dynamics of expression in prostatic tissue.

摘要

前列腺癌影响着全球数以百万计的男性。在晚期前列腺癌中,前列腺癌相关基因下调,而良性组织和低级别癌症则显示出不同的表达水平。在这项研究中,我们使用荧光原位杂交和免疫组织化学平行检测组织微阵列中组织切片的 mRNA 和蛋白质,评估了 mRNA 和蛋白质之间的空间相关性。结果表明,在前列腺组织中,mRNA 和蛋白质表达相关。此外,我们还发现,在良性导管和低级别癌症中,89%的 mRNA 富集在腔细胞的核中,在高级别癌症中,这一比例为 78%。在使用细胞的核和细胞质部分分离的 RNA 通过液滴数字聚合酶链反应 (ddPCR) 在前列腺癌细胞系 22Rv1 和 MDA PCa 2b 中验证了 mRNA 的核富集。将 mRNA 的核富集与核富集的 lncRNA 进行比较,证实了 mRNA 令人惊讶的高核保留。已经提出将 用作诊断标志物和免疫治疗的靶标,但目前对其在前列腺癌进展中的作用还缺乏全面的了解。我们的研究结果有助于更好地理解 在前列腺组织中的表达动态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae9/9865797/8d360f640a89/ijms-24-01052-g001.jpg

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