Evidence map›Paper›PMID 20196786›Full record

ArticleJournal of cellular and molecular medicine2009

Inhibition of DNA methyltransferase induces G2 cell cycle arrest and apoptosis in human colorectal cancer cells via inhibition of JAK2/STAT3/STAT5 signalling.

Hua Xiong, Zhao-Fei Chen, Qin-Chuan Liang, Wan Du, Hui-Min Chen, Wen-Yu Su, Guo-Qiang Chen, Ze-Guang Han, Jing-Yuan Fang

Abstract read
In one paragraph

Article in Journal of cellular and molecular medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
1.2field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 48 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Hua XiongDepartment of Gastroenterology, Shanghai Jiao-Tong University School of Medicine Ren-Ji Hospital, Shanghai Institute of Digestive Disease, Shanghai, China.
Zhao-Fei Chen
Qin-Chuan Liang
Wan Du
Hui-Min Chen
Wen-Yu Su
Guo-Qiang Chen
Ze-Guang Han
Jing-Yuan Fang
Shanghai Jiao Tong University · CNAir Force Medical University · CNChinese National Human Genome Center · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

DNA methyltransferase inhibitors (MTIs) have recently emerged as promising chemotherapeutic or preventive agents for cancer, despite their poorly characterized mechanisms of action. The present study shows that DNA methylation is integral to the regulation of SH2-containing protein tyrosine phosphatase 1 (SHP1) expression, but not for regulation of suppressors of cytokine signalling (SOCS)1 or SOCS3 in colorectal cancer (CRC) cells. SHP1 expression correlates with down-regulation of Janus kinase/signal transducers and activators of transcription (JAK2/STAT3/STAT5) signalling, which is mediated in part by tyrosine dephosphorylation events and modulation of the proteasome pathway. Up-regulation of SHP1 expression was achieved using a DNA MTI, 5-aza-2'-deoxycytidine (5-aza-dc), which also generated significant down-regulation of JAK2/STAT3/STAT5 signalling. We demonstrate that 5-aza-dc suppresses growth of CRC cells, and induces G2 cell cycle arrest and apoptosis through regulation of downstream targets of JAK2/STAT3/STAT5 signalling including Bcl-2, p16(ink4a), p21(waf1/cip1) and p27(kip1). Although 5-aza-dc did not significantly inhibit cell invasion, 5-aza-dc did down-regulate expression of focal adhesion kinase and vascular endothelial growth factor in CRC cells. Our results demonstrate that 5-aza-dc can induce SHP1 expression and inhibit JAK2/STAT3/STAT5 signalling. This study represents the first evidence towards establishing a mechanistic link between inhibition of JAK2/STAT3/STAT5 signalling and the anticancer action of 5-aza-dc in CRC cells that may lead to the use of MTIs as a therapeutic intervention for human colorectal cancer.

Indexed as

ApoptosisGene Expression Regulation, EnzymologicAzacitidineCell CycleCell Line, TumorColorectal NeoplasmsDecitabineDNA MethylationDNA Modification MethylasesG2 PhaseHumansJanus Kinase 2Protein Tyrosine Phosphatase, Non-Receptor Type 6STAT3 Transcription FactorSTAT5 Transcription FactorTranscription, GeneticAzacitidineDecitabineDNA Modification MethylasesJanus Kinase 2Protein Tyrosine Phosphatase, Non-Receptor Type 6STAT3 Transcription FactorSTAT5 Transcription Factor

Identifiers

PMID20196786
PMCPMC4516515
OpenAlexW2063823143

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.