title: SMG1 acts as a novel potential tumor suppressor with epigenetic inactivation in acute myeloid leukemia.
abstract: 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.
authors.affiliation: Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China. fengyinhuijing@126.com.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China. lufei1985222@163.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Lu
authors.affiliation: Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China. pengli85@163.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China. jingjing_ye@163.com.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China. jerrie981@163.com.
authors.forename: Min
authors.initials: M
authors.lastname: Ji
authors.affiliation: Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China. daoxinma@sdu.edu.cn.
authors.forename: Daoxin
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China. jichunyan@sdu.edu.cn.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Ji
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001853:Bone Marrow / Q000378:metabolism; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000235:genetics*; D000077209:Decitabine; D015536:Down-Regulation; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism*; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D058570:TOR Serine-Threonine Kinases / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*; D055815:Young Adult
chemical_list: D001374:Azacitidine; D004273:DNA, Neoplasm; D000077209:Decitabine; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D058570:TOR Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; C546842:MTOR protein, human; C514704:SMG1 protein, human