Dysregulation of PRMT1 and PRMT6, Type I arginine methyltransferases, is involved in various types of human cancers.
Protein arginine methylation is a novel post-translational modification regulating a diversity of cellular processes, including histone functions, but the roles of protein arginine methyltransferases (PRMTs) in human cancer are not well investigated. To address this issue, we first examined expression levels of genes belonging to the PRMT family and found significantly higher expression of PRMT1 and PRMT6, both of which are Type I PRMTs, in cancer cells of various tissues than in non-neoplastic cells. Abrogation of the expression of these genes with specific siRNAs significantly suppressed growth of bladder and lung cancer cells. Expression profile analysis using the cells transfected with the siRNAs indicated that PRMT1 and PRMT6 interplay in multiple pathways, supporting regulatory roles in the cell cycle, RNA processing and also DNA replication that are fundamentally important for cancer cell proliferation. Furthermore, we demonstrated that serum asymmetric dimethylarginine (ADMA) levels of a number of cancer cases are significantly higher than those of nontumor control cases. In summary, our results suggest that dysregulation of PRMT1 and PRMT6 can be involved in human carcinogenesis and that these Type I arginine methyltransferases are good therapeutic targets for various types of cancer.
Yoshimatsu
Masanori
M
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Minato-Ku, Tokyo, Japan.
Toyokawa
Gouji
G
Hayami
Shinya
S
Unoki
Motoko
M
Tsunoda
Tatsuhiko
T
Field
Helen I
HI
Kelly
John D
JD
Neal
David E
DE
Maehara
Yoshihiko
Y
Ponder
Bruce A J
BA
Nakamura
Yusuke
Y
Hamamoto
Ryuji
R
D000873:Anthracenes; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology; D002455:Cell Division; D045744:Cell Line, Tumor; D004261:DNA Replication; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D009369:Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011407:Propane / Q000031:analogs & derivatives / Q000097:blood; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
D000873:Anthracenes; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C018524:N,N-dimethylarginine; D001120:Arginine; C099988:PRMT1 protein, human; C447833:PRMT6 protein, human; D011484:Protein-Arginine N-Methyltransferases; D011407:Propane