Isin Hüsniye, Özgür Emre, Talu Canan Kelten, Trabulus Didem Can, Karaçetin Didem, Gezer Ugur
Department of Basic Oncology, Oncology Institute, Istanbul University, Istanbul 34093, Turkey.
Department of Pathology, Istanbul Training and Research Hospital, University of Health Sciences, Istanbul 34096, Turkey.
Biomed Rep. 2020 Oct;13(4):29. doi: 10.3892/br.2020.1336. Epub 2020 Jul 23.
Breast cancer is the most common type of cancer in women worldwide. Triple methylation of H4 lysine 20 (H4K20me3), a key component of epigenetic regulation of genomic integrity, is catalyzed by the methyltransferase, SUV420H2. Data on the expression status of SUV420H2 in breast cancer are limited. In the present study, the influence of SUV420H2 suppression on the proliferation of breast cancer cells was experimentally investigated. Subsequently, SUV420H2 expression was assessed in resectable breast cancer along with H4K20me3 status. SUV420H2 expression was knocked down in breast cells using small interfering RNA oligonucleotides. SUV420H2 expression was determined semi-quantitatively at the mRNA level. H4K20me3 was measured on extracted histone proteins using an approach similar to ELISA. Suppression of the SUV420H2 gene resulted in increased cell proliferation. Although the median SUV420H2 expression values were similar in tumor tissues and non-cancerous regions in the entire cohort (0.0022 and 0.0015, respectively; P=0.46), there was a notable difference in expression between tumor tissues and the adjacent non-cancerous region in the majority of patients. Increased SUV420H2 expression in tumors compared with healthy tissue was predominantly observed in patients with early-stage breast cancer, whereas reduced SUV420H2 expression was observed in tumors more frequently in patients with advanced stage diseases. There was no association between SUV420H2 expression and the tissue levels of H4K20me3. The results showed that SUV420H2 exhibited anti-proliferative activity , and exhibits a heterogeneous expression pattern in breast cancer tissues.
乳腺癌是全球女性中最常见的癌症类型。组蛋白H4赖氨酸20位点的三甲基化（H4K20me3）是基因组完整性表观遗传调控的关键组成部分，由甲基转移酶SUV420H2催化。关于SUV420H2在乳腺癌中表达状态的数据有限。在本研究中，通过实验研究了SUV420H2抑制对乳腺癌细胞增殖的影响。随后，评估了可切除乳腺癌中SUV420H2的表达以及H4K20me3的状态。使用小干扰RNA寡核苷酸敲低乳腺细胞中SUV420H2的表达。在mRNA水平上半定量测定SUV420H2的表达。使用类似于ELISA的方法在提取的组蛋白上测量H4K20me3。SUV420H2基因的抑制导致细胞增殖增加。虽然在整个队列中肿瘤组织和非癌区域的SUV420H2表达中值相似（分别为0.0022和0.0015；P = 0.46），但在大多数患者中肿瘤组织与相邻非癌区域之间的表达存在显著差异。与健康组织相比，肿瘤中SUV420H2表达增加主要在早期乳腺癌患者中观察到，而在晚期疾病患者的肿瘤中更频繁地观察到SUV420H2表达降低。SUV420H2表达与H4K20me3的组织水平之间没有关联。结果表明，SUV420H2具有抗增殖活性，并且在乳腺癌组织中表现出异质性表达模式。
