Department of Urology, Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
Kaohsiung J Med Sci. 2023 Jun;39(6):576-586. doi: 10.1002/kjm2.12661. Epub 2023 Feb 24.
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.
前列腺癌是男性最常见的癌症之一。本研究旨在探讨 euchromatic histone lysine methyltransferase 2 (EHMT2) 和内质网蛋白 29 (ERP29) 在前列腺癌细胞放射抵抗进展中的作用。采用定量逆转录-聚合酶链反应和蛋白质印迹法检测前列腺癌细胞中 EHMT2 和 ERP29 的表达,并探讨 EHMT2 和 ERP29 之间的相互作用。采用噻唑蓝比色法和集落形成实验检测转染细胞在 X 射线照射下的增殖情况。采用流式细胞术检测 X 射线照射下转染细胞的凋亡情况。将稳定转染 sh-ERP29 或 sh-NC 的前列腺癌细胞(DU145)皮下注射裸鼠。通过 X 射线照射评估 ERP29 表达对裸鼠放射抵抗的影响。在放射抵抗进展过程中,前列腺癌细胞中 EHMT2 的表达上调,而 ERP29 的表达下调。EHMT2 下调抑制了 DU145 和雄激素敏感前列腺癌细胞(LNCaP)的放射抵抗。在照射后的 DU145 细胞中,EHMT2 抑制降低了集落数量并加速了细胞凋亡。EHMT2 通过上调 H3K9me2 和下调 H3K4me3 抑制 ERP29 的转录,从而调节前列腺癌细胞的放射抵抗。此外,ERP29 的下调促进了裸鼠前列腺癌细胞放射抵抗的进展。EHMT2 通过抑制 ERP29 的转录促进前列腺癌细胞的放射抵抗。