PMID- 22955854
OWN - NLM
STAT- MEDLINE
DCOM- 20121211
LR  - 20220318
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 107
IP  - 8
DP  - 2012 Oct 9
TI  - Clinical significance of miR-144-ZFX axis in disseminated tumour cells in bone 
      marrow in gastric cancer cases.
PG  - 1345-53
LID - 10.1038/bjc.2012.326 [doi]
AB  - BACKGROUND: We previously reported that bone marrow (BM) was a homing site for 
      gastric cancer (GC) cells leading to haematogenous metastases. There has been 
      little study that microRNAs regulated pathways in malignant cells or host cells 
      in BM, and thereby regulated the progression of GC. METHODS: Both microRNA 
      microarray and gene expression microarray analyses of total RNA from BM were 
      conducted, comparing five early and five advanced GC patients. We focused on 
      miR-144-ZFX axis as a candidate BM regulator of GC progression and validated the 
      origin of the microRNA expression in diverse cell fractions (EpCAM(+)CD45(-), 
      EpCAM(-)CD45(+), and CD14(+)) by magnetic-activated cell sorting (MACS). RESULTS: 
      Quantitative reverse-transcriptase (RT)-PCR analysis validated diminished miR-144 
      expression in stage IV GC patients with respect to stage I GC patients (t-test, 
      P=0.02), with an inverse correlation to ZFX (ANOVA, P<0.01). Luciferase reporter 
      assays in five GC cell lines indicated their direct binding and validated by 
      western blotting. Pre-miR144 treatment and the resultant repression of ZFX in GC 
      cell lines moderately upregulated their susceptibility to 5-fluorouracil 
      chemotherapy. In MACS-purified BM fractions, the level of miR-144 expression was 
      significantly diminished in disseminated tumour cell fraction (P=0.0005). 
      Diminished miR-144 expression in 93 cases of primary GC indicated poor prognosis. 
      CONCLUSION: We speculate that disseminated cancer cells could survive in BM when 
      low expression of miR-144 permits upregulation of ZFX. The regulation of the 
      miR-144-ZFX axis in cancer cells has a key role in the indicator of the 
      progression of GC cases.
FAU - Akiyoshi, S
AU  - Akiyoshi S
AD  - Department of Surgery, Kyushu University Beppu Hospital, Tsurumihara, Japan.
FAU - Fukagawa, T
AU  - Fukagawa T
FAU - Ueo, H
AU  - Ueo H
FAU - Ishibashi, M
AU  - Ishibashi M
FAU - Takahashi, Y
AU  - Takahashi Y
FAU - Fabbri, M
AU  - Fabbri M
FAU - Sasako, M
AU  - Sasako M
FAU - Maehara, Y
AU  - Maehara Y
FAU - Mimori, K
AU  - Mimori K
FAU - Mori, M
AU  - Mori M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120906
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (MIRN144 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (zinc finger protein, X-linked)
SB  - IM
MH  - Bone Marrow/*metabolism/pathology
MH  - Disease Progression
MH  - Gene Expression Profiling
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Kruppel-Like Transcription Factors/*genetics
MH  - MicroRNAs/*genetics
MH  - Neoplastic Cells, Circulating
MH  - Oligonucleotide Array Sequence Analysis
MH  - Prognosis
MH  - Stomach Neoplasms/*genetics/pathology
PMC - PMC3494440
EDAT- 2012/09/08 06:00
MHDA- 2012/12/12 06:00
PMCR- 2013/10/09
CRDT- 2012/09/08 06:00
PHST- 2012/09/08 06:00 [entrez]
PHST- 2012/09/08 06:00 [pubmed]
PHST- 2012/12/12 06:00 [medline]
PHST- 2013/10/09 00:00 [pmc-release]
AID - bjc2012326 [pii]
AID - 10.1038/bjc.2012.326 [doi]
PST - ppublish
SO  - Br J Cancer. 2012 Oct 9;107(8):1345-53. doi: 10.1038/bjc.2012.326. Epub 2012 Sep 
      6.