文章目录

丝氨酸羟甲基转移酶-2 （SHMT2）通过表观遗传肿瘤抑制基因沉默引发淋巴瘤的发展

原文发布日期：2020-06-22

英文摘要：

摘要翻译：

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丝氨酸羟甲基转移酶-2 （SHMT2）通过表观遗传肿瘤抑制基因沉默引发淋巴瘤的发展

The serine hydroxymethyltransferase-2 (SHMT2) initiates lymphoma development through epigenetic tumor suppressor silencing

原文发布日期：2020-06-22

英文摘要：

Cancer cells adapt their metabolic activities to support growth and proliferation. However, increased activity of metabolic enzymes is not usually considered an initiating event in the malignant process. Here, we investigate the possible role of the enzyme serine hydroxymethyltransferase-2 (SHMT2) in lymphoma initiation. SHMT2 localizes to the most frequent region of copy number gains at chromosome 12q14.1 in lymphoma. Elevated expression of SHMT2 cooperates with BCL2 in lymphoma development; loss or inhibition of SHMT2 impairs lymphoma cell survival. SHMT2 catalyzes the conversion of serine to glycine and produces an activated one-carbon unit that can be used to support S-adenosyl methionine synthesis. SHMT2 induces changes in DNA and histone methylation patterns leading to promoter silencing of previously uncharacterized mutational genes, such as SASH1 and PTPRM. Together, our findings reveal that amplification of SHMT2 in cooperation with BCL2 is sufficient in the initiation of lymphomagenesis through epigenetic tumor suppressor silencing.

摘要翻译：

癌细胞会通过调整代谢活动来支持其生长和增殖。然而，代谢酶活性的升高通常并不是恶性过程的启动事件之一。在本研究中，我们探讨了丝氨酸羟氨甲酰转移酶2（SHMT2）在淋巴癌发生中的潜在作用。SHMT2定位在淋巴癌中最常见的拷贝数增减区——染色体12q14.1区域。SHMT2的高表达与BCL2共同促进淋巴癌的发展；SHMT2的缺失或抑制会损害淋巴癌细胞的存活率。SHMT2催化将丝氨酸转化为甘氨酸，并产生一种活性一碳单位，这种单个单位可用于支持S-腺苷甲硫氨酸的合成。SHMT2诱导DNA和histone 甲基化模式的变化，导致一些先前未被描述过的突变基因（如SASH1和PTPRM）的沉默。综上所述，我们的研究发现，SHMT2与BCL2在合作下通过表观遗传学肿瘤 suppressor 潜力沉默是淋巴癌发生的一个充分机制。