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慢性间歇性低氧处理的去势抵抗性前列腺癌细胞系的转录组分析

Transcriptomic Profiling Analysis of Castration-Resistant Prostate Cancer Cell Lines Treated with Chronic Intermittent Hypoxia.

作者信息

Lee Chung Lyul, Lee Minji, Lee Ji Yong, Hong Sin-Hyoung, Yang Seung Woo, Min Ji-Hyeon, Lee Dong-Eon, Baek Joonyoung, Kim Chanseul, Lim Jae Sung, Song Ki Hak, Shin Ju Hyun, Kim Gun-Hwa

机构信息

Department of Urology, College of Medicine, Chungnam National University, 266, Munhwa-ro, Jung-gu, Daejeon 35015, Korea.

Department of Bio-Analytical Science, University of Science and Technology (UST), Daejeon 34113, Korea.

出版信息

Cancers (Basel). 2022 Aug 16;14(16):3959. doi: 10.3390/cancers14163959.

DOI:10.3390/cancers14163959
PMID:36010952
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9406188/
Abstract

Castration-resistant prostate cancer (CRPC) is still a major concern in men's health, with 375,000 cancer deaths annually. Hypoxia, which is a marked characteristic of advanced solid tumors, has been suggested to induce prostate cancer towards CRPC, metastasis and treatment resistance. To evaluate the effect of hypoxia on prostate cancer, two and five cycles of hypoxia and reoxygenation were administered using 22Rv1 cell lines and denominated as 22Rv1-CI and 22Rv1-PCI, respectively. Cancer cell migration was promoted in 22Rv1-CI compared to controls, and the expression of COL13A1 was significantly up-regulated in 22Rv1-CI according to differentially expressed gene analysis of RNA sequencing among groups. Cancer cell migration was impeded in a wound healing assay after transfecting si-COL13A1. Moreover, the expression of COL13A1 was also higher in the cell line originating from bone metastatic prostate cancer compared to other cell lines. Using the open database GEO, we also confirmed that the expression of COL13A1 was higher in bone metastatic prostate cancer tissue than in localized prostate cancer tissue in patients. Therefore, COL13A1 may be closely related to the bony metastasis of prostate cancer, and our findings may provide valuable information on the pathophysiology of the metastatic niche induced by hypoxia in patients with CRPC.

摘要

去势抵抗性前列腺癌（CRPC）仍是男性健康的一大关注点，每年有37.5万人死于该癌症。缺氧是晚期实体瘤的一个显著特征，有人认为它会促使前列腺癌发展为CRPC、发生转移并产生治疗抵抗。为了评估缺氧对前列腺癌的影响，使用22Rv1细胞系进行了两个周期和五个周期的缺氧及复氧处理，分别命名为22Rv1-CI和22Rv1-PCI。与对照组相比，22Rv1-CI中的癌细胞迁移得到促进，并且根据各组之间RNA测序的差异表达基因分析，22Rv1-CI中COL13A1的表达显著上调。转染si-COL13A1后，在伤口愈合试验中癌细胞迁移受到阻碍。此外，与其他细胞系相比，源自骨转移性前列腺癌的细胞系中COL13A1的表达也更高。利用公开数据库GEO，我们还证实，在患者中，骨转移性前列腺癌组织中COL13A1的表达高于局限性前列腺癌组织。因此，COL13A1可能与前列腺癌的骨转移密切相关，我们的研究结果可能为CRPC患者缺氧诱导的转移微环境的病理生理学提供有价值的信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b8e/9406188/34905bf64c39/cancers-14-03959-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b8e/9406188/72f068c4fb67/cancers-14-03959-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b8e/9406188/bccdae03ee76/cancers-14-03959-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b8e/9406188/85a1e66c5e22/cancers-14-03959-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b8e/9406188/12af1e097e31/cancers-14-03959-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b8e/9406188/12a47eff994d/cancers-14-03959-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b8e/9406188/472461588577/cancers-14-03959-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b8e/9406188/34905bf64c39/cancers-14-03959-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b8e/9406188/72f068c4fb67/cancers-14-03959-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b8e/9406188/bccdae03ee76/cancers-14-03959-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b8e/9406188/85a1e66c5e22/cancers-14-03959-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b8e/9406188/12af1e097e31/cancers-14-03959-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b8e/9406188/12a47eff994d/cancers-14-03959-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b8e/9406188/472461588577/cancers-14-03959-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b8e/9406188/34905bf64c39/cancers-14-03959-g007.jpg

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Adaptation to Chronic-Cycling Hypoxia Renders Cancer Cells Resistant to MTH1-Inhibitor Treatment Which Can Be Counteracted by Glutathione Depletion.慢性循环低氧适应使癌细胞对 MTH1 抑制剂治疗产生抗性，而谷胱甘肽耗竭可逆转这种抗性。
Cells. 2021 Nov 5;10(11):3040. doi: 10.3390/cells10113040.
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Prognostic Value of Highly Expressed Type VII Collagen (COL7A1) in Patients With Gastric Cancer.
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Pathol Oncol Res. 2021 Aug 26;27:1609860. doi: 10.3389/pore.2021.1609860. eCollection 2021.
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Lancet. 2021 Sep 18;398(10305):1075-1090. doi: 10.1016/S0140-6736(21)00950-8. Epub 2021 Aug 6.
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