SMG1 acts as a novel potential tumor suppressor with epigenetic inactivation in acute myeloid leukemia.
SMG1 acts as a novel potential tumor suppressor with epigenetic inactivation in acute myeloid leukemia.
复制标题
SMG1 作为一种新型潜在肿瘤抑制因子，在急性髓系白血病中具有表观遗传失活作用
DOI：
10.3390/ijms150917065
复制
发表时间：
2014-09-25
影响因子：
5.6
通讯作者：
Ji C
中科院分区：
文献类型：
--
作者：
Du Y;Lu F;Li P;Ye J;Ji M;Ma D;Ji C
对生殖器有形态发生作用的抑制因子家族成员（SMG 1）属于磷酸肌醇3-激酶相关激酶家族，是参与无义介导的mRNA降解的主要激酶。最近，SMG 1被认为是一种新的潜在的肿瘤抑制基因，特别是在缺氧肿瘤中。为了研究SMG 1在急性髓系白血病（AML）中的功能，我们进行了甲基化特异性聚合酶链反应，发现SMG 1在启动子区高甲基化。SMG 1基因甲基化在AML中的阳性率为66%（33/50），而在正常对照组中无一例（0/14）。SMG 1 mRNA在高甲基化状态的AML患者中下调，而在无甲基化状态的患者中易于表达。此外，用去甲基化剂5-氮杂-2 '-脱氧胞苷（地西他滨）处理AML细胞通过逆转SMG 1甲基化状态和恢复SMG 1表达来抑制AML细胞生长并诱导细胞凋亡。另一方面，通过RNA干扰敲低SMG 1抑制细胞凋亡。AML患者中SMG 1和mTOR的表达水平呈负相关，提示SMG 1和mTOR可能通过拮抗作用调节AML细胞的生长。总之，我们的研究结果表明，SMG 1作为一个潜在的肿瘤抑制与AML的表观遗传调控。
Suppressor with morphogenetic effect on genitalia family member (SMG1) belongs to a family of phosphoinositide 3-kinase-related kinases and is the main kinase involved in nonsense-mediated mRNA decay. Recently, SMG1 was suggested as a novel potential tumor suppressor gene, particularly in hypoxic tumors. To investigate the function of SMG1 in acute myeloid leukemia (AML), we performed methylation-specific polymerase chain reaction and found that SMG1 was hypermethylated in the promoter region. SMG1 hypermethylation was found in 66% (33/50) of AML samples compared with none (0/14) of the normal controls. SMG1 mRNA was down-regulated in AML patients with hypermethylation status whereas it was readily expressed in patients without methylation. Moreover, treatment of AML cells with demethylating agent 5-aza-2'-deoxycytidine (decitabine) inhibited AML cell growth and induced apoptosis by reversing SMG1 methylation status and restoring SMG1 expression. On the other hand, knockdown of SMG1 by RNA interference inhibited apoptosis. We also found that mTOR expression level was negatively correlated to SMG1 expression in AML patients which indicated that SMG1 and mTOR maybe act antagonistically to regulate AML cell growth. In conclusion, our results indicate that SMG1 acts as a potential tumor suppressor with epigenetic regulation in AML.
登录
查看更多内容
DOI：
10.1056/nejmoa1005143
发表时间：
2010-12-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ley TJ;Ding L;Walter MJ;McLellan MD;Lamprecht T;Larson DE;Kandoth C;Payton JE;Baty J;Welch J;Harris CC;Lichti CF;Townsend RR;Fulton RS;Dooling DJ;Koboldt DC;Schmidt H;Zhang Q;Osborne JR;Lin L;O'Laughlin M;McMichael JF;Delehaunty KD;McGrath SD;Fulton LA;Magrini VJ;Vickery TL;Hundal J;Cook LL;Conyers JJ;Swift GW;Reed JP;Alldredge PA;Wylie T;Walker J;Kalicki J;Watson MA;Heath S;Shannon WD;Varghese N;Nagarajan R;Westervelt P;Tomasson MH;Link DC;Graubert TA;DiPersio JF;Mardis ER;Wilson RK
通讯作者：
Wilson RK
影响因子：
3.5
作者：
Tawfik, Bernard;Sliesoraitis, Sarunas;Lyerly, Susan;Klepin, Heidi D.;Lawrence, Julia;Isom, Scott;Ellis, Leslie R.;Manuel, Megan;Dralle, Sarah;Berenzon, Dmitriy;Powell, Bayard L.;Pardee, Timothy
通讯作者：
Pardee, Timothy
影响因子：
4.3
作者：
Gewandter, Jennifer S.;Bambara, Robert A.;O'Reilly, Michael A.
通讯作者：
O'Reilly, Michael A.
影响因子：
45.3
作者：
Marcucci, Guido;Yan, Pearlly;Bloomfield, Clara D.
通讯作者：
Bloomfield, Clara D.
影响因子：
4.8
作者：
Oliveira, Vasco;Romanow, William J.;Abraham, Robert T.
通讯作者：
Abraham, Robert T.