常染色组蛋白赖氨酸甲基转移酶2通过抑制内质网蛋白29的转录促进前列腺癌的放射耐药。

IF 2.7 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Kaohsiung Journal of Medical Sciences Pub Date : 2023-06-01 DOI:10.1002/kjm2.12661
Zhi-Chao Huang, Jun Huang, Chang-Kun Huang, Yi Hou, Bin Zhu
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引用次数: 0

摘要

前列腺癌是男性最常见的癌症之一。本研究旨在探讨常染色质组蛋白赖氨酸甲基转移酶2 (EHMT2)和内质网蛋白29 (ERP29)在前列腺癌放射耐药进展中的作用。采用定量逆转录-聚合酶链反应和western blotting检测EHMT2和ERP29在前列腺癌细胞中及放射耐药过程中的表达,并探讨EHMT2与ERP29的相互作用。用甲基噻唑四氮唑和集落形成试验测定转染细胞在x射线照射下的增殖。用流式细胞术分析转染后的细胞在x射线照射下的凋亡情况。裸鼠皮下注射稳定转染sh-ERP29或sh-NC的前列腺癌(DU145)细胞。采用x射线照射法观察ERP29表达对裸鼠辐射抗性的影响。在前列腺癌细胞放射耐药过程中,EHMT2表达上调,ERP29表达下调。EHMT2下调可抑制DU145和雄激素敏感前列腺癌(LNCaP)细胞的放射耐药。在辐照的DU145细胞中,EHMT2抑制减少了菌落数量,加速了细胞凋亡。EHMT2通过上调H3K9me2和下调H3K4me3来抑制ERP29的转录,从而调节前列腺癌细胞的放射耐药。此外,ERP29的下调促进了裸鼠前列腺癌细胞放射耐药的进展。EHMT2通过抑制ERP29转录促进前列腺癌细胞的放射耐药。
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Euchromatic histone lysine methyltransferase 2 facilitates radioresistance in prostate cancer by repressing endoplasmic reticulum protein 29 transcription.

Prostate cancer is one of the most common cancers in men. This study was conducted to investigate the role of euchromatic histone lysine methyltransferase 2 (EHMT2) and endoplasmic reticulum protein 29 (ERP29) in the progression of radioresistance in prostate cancer. The expression of EHMT2 and ERP29 in prostate cancer cells and during the progression of radioresistance was detected using quantitative reverse transcription-polymerase chain reaction and western blotting, and the interaction between EHMT2 and ERP29 was investigated. The proliferation of transfected cells under x-ray irradiation was determined using the methyl thiazolyl tetrazolium and colony formation assays. Flow cytometry was used to analyze the apoptosis of the transfected cells under x-ray irradiation. Nude mice were subcutaneously injected with prostate cancer (DU145) cells stably transfected with sh-ERP29 or sh-NC. The effect of ERP29 expression on radioresistance in nude mice was assessed by x-ray irradiation. The expression of EHMT2 was upregulated and that of ERP29 was downregulated in prostate cancer cells during radioresistance progression. EHMT2 downregulation suppressed radioresistance in DU145 and androgen-sensitive prostate cancer (LNCaP) cells. In irradiated DU145 cells, EHMT2 inhibition decreased the number of colonies and accelerated apoptosis. The transcription of ERP29 was suppressed by EHMT2 by upregulating H3K9me2 and downregulating H3K4me3, thereby regulating radioresistance in prostate cancer cells. In addition, the downregulation of ERP29 promoted the progression of radioresistance in prostate cancer cells in nude mice. EHMT2 promotes radioresistance in prostate cancer cells by repressing ERP29 transcription.

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来源期刊
Kaohsiung Journal of Medical Sciences
Kaohsiung Journal of Medical Sciences 医学-医学:研究与实验
CiteScore
5.60
自引率
3.00%
发文量
139
审稿时长
4-8 weeks
期刊介绍: Kaohsiung Journal of Medical Sciences (KJMS), is the official peer-reviewed open access publication of Kaohsiung Medical University, Taiwan. The journal was launched in 1985 to promote clinical and scientific research in the medical sciences in Taiwan, and to disseminate this research to the international community. It is published monthly by Wiley. KJMS aims to publish original research and review papers in all fields of medicine and related disciplines that are of topical interest to the medical profession. Authors are welcome to submit Perspectives, reviews, original articles, short communications, Correspondence and letters to the editor for consideration.
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