PMID- 25928165
OWN - NLM
STAT- MEDLINE
DCOM- 20160204
LR  - 20220608
IS  - 1476-4598 (Electronic)
IS  - 1476-4598 (Linking)
VI  - 14
DP  - 2015 Apr 19
TI  - Long noncoding RNA, CCDC26, controls myeloid leukemia cell growth through 
      regulation of KIT expression.
PG  - 90
LID - 10.1186/s12943-015-0364-7 [doi]
LID - 90
AB  - BACKGROUND: Accumulating evidence suggests that some long noncoding RNAs 
      (lncRNAs) are involved in certain diseases, such as cancer. The lncRNA, CCDC26, 
      is related to childhood acute myeloid leukemia (AML) because its copy number is 
      altered in AML patients. RESULTS: We found that CCDC26 transcripts were abundant 
      in the nuclear fraction of K562 human myeloid leukemia cells. To examine the 
      function of CCDC26, gene knockdown (KD) was performed using short hairpin RNAs 
      (shRNAs), and four KD clones, in which CCDC26 expression was suppressed to 1% of 
      its normal level, were isolated. This down-regulation included suppression of 
      CCDC26 intron-containing transcripts (the CCDC26 precursor mRNA), indicating that 
      transcriptional gene suppression (TGS), not post-transcriptional suppression, was 
      occurring. The shRNA targeting one of the two CCDC26 splice variants also 
      suppressed the other splice variant, which is further evidence for TGS. Growth 
      rates of KD clones were reduced compared with non-KD control cells in media 
      containing normal or high serum concentrations. In contrast, enhanced growth 
      rates in media containing much lower serum concentrations and increased survival 
      periods after serum withdrawal were observed for KD clones. DNA microarray and 
      quantitative polymerase chain reaction screening for differentially expressed 
      genes between KD clones and non-KD control cells revealed significant 
      up-regulation of the tyrosine kinase receptor, KIT, hyperactive mutations of 
      which are often found in AML. Treatment of KD clones with ISCK03, a KIT-specific 
      inhibitor, eliminated the increased survival of KD clones in the absence of 
      serum. CONCLUSIONS: We suggest that CCDC26 controls growth of myeloid leukemia 
      cells through regulation of KIT expression. A KIT inhibitor might be an effective 
      treatment against the forms of AML in which CCDC26 is altered.
FAU - Hirano, Tetsuo
AU  - Hirano T
AD  - Domain of Life Sciences, Graduate School of Integrated Arts and Sciences, 
      Hiroshima University, 1-7-1 Kagamiyama, Higashihiroshima, Hiroshima, 739-8521, 
      Japan. thirano@hiroshima-u.ac.jp.
FAU - Yoshikawa, Ryoko
AU  - Yoshikawa R
AD  - Domain of Life Sciences, Graduate School of Integrated Arts and Sciences, 
      Hiroshima University, 1-7-1 Kagamiyama, Higashihiroshima, Hiroshima, 739-8521, 
      Japan. m142847@hiroshima-u.ac.jp.
FAU - Harada, Hironori
AU  - Harada H
AD  - Department of Hematology, Juntendo University School of Medicine, 2-1-1 Hongo, 
      Bunkyo-ku, Tokyo, 113-8421, Japan. hharada@juntendo.ac.jp.
FAU - Harada, Yuka
AU  - Harada Y
AD  - Department of Hematology, Juntendo University School of Medicine, 2-1-1 Hongo, 
      Bunkyo-ku, Tokyo, 113-8421, Japan. ykharada@juntendo.ac.jp.
FAU - Ishida, Atsuhiko
AU  - Ishida A
AD  - Domain of Life Sciences, Graduate School of Integrated Arts and Sciences, 
      Hiroshima University, 1-7-1 Kagamiyama, Higashihiroshima, Hiroshima, 739-8521, 
      Japan. aishida@hiroshima-u.ac.jp.
FAU - Yamazaki, Takeshi
AU  - Yamazaki T
AD  - Domain of Life Sciences, Graduate School of Integrated Arts and Sciences, 
      Hiroshima University, 1-7-1 Kagamiyama, Higashihiroshima, Hiroshima, 739-8521, 
      Japan. takey@hiroshima-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150419
PL  - England
TA  - Mol Cancer
JT  - Molecular cancer
JID - 101147698
RN  - 0 (4-t-butylphenyl-N-(4-imidazol-1-ylphenyl)sulfonamide)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Imidazoles)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Sulfonamides)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
SB  - IM
MH  - Base Sequence
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Clone Cells
MH  - Culture Media, Serum-Free
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation, Leukemic/drug effects
MH  - Gene Knockdown Techniques
MH  - Gene Silencing/drug effects
MH  - Genetic Loci
MH  - Genetic Vectors/metabolism
MH  - HL-60 Cells
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - K562 Cells
MH  - Leukemia, Myeloid, Acute/*genetics/*pathology
MH  - Molecular Sequence Data
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Proto-Oncogene Proteins c-kit/antagonists & inhibitors/*genetics/metabolism
MH  - RNA, Long Noncoding/genetics/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Serum
MH  - Sulfonamides/pharmacology
PMC - PMC4423487
EDAT- 2015/05/01 06:00
MHDA- 2016/02/05 06:00
PMCR- 2015/04/19
CRDT- 2015/05/01 06:00
PHST- 2014/12/12 00:00 [received]
PHST- 2015/04/09 00:00 [accepted]
PHST- 2015/05/01 06:00 [entrez]
PHST- 2015/05/01 06:00 [pubmed]
PHST- 2016/02/05 06:00 [medline]
PHST- 2015/04/19 00:00 [pmc-release]
AID - 10.1186/s12943-015-0364-7 [pii]
AID - 364 [pii]
AID - 10.1186/s12943-015-0364-7 [doi]
PST - epublish
SO  - Mol Cancer. 2015 Apr 19;14:90. doi: 10.1186/s12943-015-0364-7.