BMI1 and Mel-18 oppositely regulate carcinogenesis and progression of gastric cancer

Zhang, Xiao Wei; Sheng, Ya Ping; Li, Qian; Qin, Wei; Lu, Yao; Cheng, Yu; Liu, Bingya; Zhang, Feng Chun; Jin, Li; Dimri, Goberdhan P.; Guo, Wei

doi:10.1186/1476-4598-9-40

Cited by 83 publications

(84 citation statements)

References 35 publications

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“…Although a repression of pro-proliferative miRNA loci is consistent with a general role of PcG proteins as tumor suppressors (Classen et al 2009;Martinez and Cavalli 2010), growth effects of PcG proteins seem to be rather diverse and context-dependent when examined in detail (Beuchle et al 2001;Saj et al 2010). Accordingly, PcG proteins in mammals also show antagonistic proliferative functions (Lessard et al 1999;Zhang et al 2010a), indicating a complex regulatory relationship to growth control in both organisms. In stark contrast to bantam, mir-8 seems to be functionally conserved and controls growth via the PI3K pathway in flies as in humans (Hyun et al 2009)-possibly engaging in a regulatory feedback, as also demonstrated for mir-214 ( Juan et al 2009;Iliopoulos et al 2010).…”

Section: Prc1 Binds Promoters Of Coding and Noncoding Genesmentioning

confidence: 91%

Polycomb preferentially targets stalled promoters of coding and noncoding transcripts

Enderle

Beisel²,

Stadler³

et al. 2010

Genome Res.

152

187

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The Polycomb group (PcG) and Trithorax group (TrxG) of proteins are required for stable and heritable maintenance of repressed and active gene expression states. Their antagonistic function on gene control, repression for PcG and activity for TrxG, is mediated by binding to chromatin and subsequent epigenetic modification of target loci. Despite our broad knowledge about composition and enzymatic activities of the protein complexes involved, our understanding still lacks important mechanistic detail and a comprehensive view on target genes. In this study we use an extensive data set of ChIP-seq, RNA-seq, and genome-wide detection of transcription start sites (TSSs) to identify and analyze thousands of binding sites for the PcG proteins and Trithorax from a Drosophila S2 cell line. In addition of finding a preference for stalled promoter regions of annotated genes, we uncover many intergenic PcG binding sites coinciding with nonannotated TSSs. Interestingly, this set includes previously unknown promoters for primary transcripts of microRNA genes, thereby expanding the scope of Polycomb control to noncoding RNAs essential for development, apoptosis, and growth.

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Section: Prc1 Binds Promoters Of Coding and Noncoding Genesmentioning

confidence: 91%

Polycomb preferentially targets stalled promoters of coding and noncoding transcripts

Enderle

Beisel²,

Stadler³

et al. 2010

Genome Res.

152

187

View full text Add to dashboard Cite

show abstract

“…In addition to the proposed role for Bmi1 as a key regulator of cell growth control/senescence mechanisms, accumulating evidence supports the role of Bmi1 in tumorigenesis. Bmi1 is overexpressed in a variety of human cancers and its overexpression was found to be correlated with tumor progression in CRC (5-7) and other gastrointestinal cancers, including esophageal squamous cell carcinoma (8,9), pancreatic cancer (10) and gastric cancer (11), indicating its functional and prognostic role in gastrointestinal cancer patients. The Bmi1 autoantibody in the serum has also been suggested as a minimally invasive biomarker for the prognosis of nasopharyngeal (12), esophageal squamous cell (8) and cervical carcinoma (13).…”

Section: Introductionmentioning

confidence: 99%

Plasma Bmi1 mRNA as a potential prognostic biomarker for distant metastasis in colorectal cancer patients

Pun¹,

Chan²,

Chun³

et al. 2014

Molecular and Clinical Oncology

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Abstract. Bmi1 is overexpressed in gastrointestinal cancers, including colorectal cancer (CRC); however, its role as a non-invasive biomarker in CRC has not been established. The aim of this study was to compare the plasma Bmi1 mRNA levels prior to and following curative resection of the primary tumor in CRC patients and to determine their association with the clinicopathological parameters. The plasma Bmi1 mRNA level was measured by quantitative polymerase chain reaction and expressed as cycle threshold value. There was no significant difference between the overall pre-and postoperative plasma Bmi1 mRNA level (31.73±2.63 vs. 31.93±2.88, respectively; P=0.614) in 45 CRC patients. However, when grouped into non-metastatic and metastatic CRC patients, the postoperative Bmi1 transcript level was found to be significantly lower compared to the preoperative level in patients with non-metastatic CRC (32.13±2.677 31.44±2.764, respectively; P=0.041), whereas there was a trend towards a higher postoperative Bmi1 transcript level compared to the preoperative level in the metastatic counterpart (30.85±3.916 vs. 33.27±0.718, respectively; P=0.164). Furthermore, when the patients were categorized into two groups according to their plasma Bmi1 postoperative vs. preoperative level status, we observed that patients without a reduction in the postoperative plasma Bmi1 mRNA levels exhibited a significantly higher rate of distant metastasis following primary resection (P=0.017) and a significantly worse prognosis regarding disease-free survival (P=0.016) when compared to the reduced postoperative plasma Bmi1 level counterparts. In conclusion, plasma Bmi1 mRNA levels may serve as a non-invasive biomarker for monitoring occult metastasis and predicting the development of distant metastasis. IntroductionColorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females, with >1.2 million new cancer cases and 608,700 deaths estimated to have occurred in 2008 (1). Recent advances in therapeutic strategies and surgical techniques have significantly improved the prognosis of CRC patients with primary disease; however, metastasis is a major concern for CRC patients and physicians. Thirty-five percent of CRC patients have metastatic tumors at the time of diagnosis and 33-50% of the patients without metastases will progress to stage IV during the course of their disease (1,2). Hence, it is necessary to develop prominent biomarkers for detecting the presence of occult metastasis, as well as for predicting the development of future metastasis, which may provide a useful reference for the therapeutic management of CRC patients.Potential stem cell marker, Bmi1, is a member of the polycomb-repressive complex 1, with a key role in gene silencing through chromatin modifications (3,4). In addition to the proposed role for Bmi1 as a key regulator of cell growth control/senescence mechanisms, accumulating evidence supports the role of Bmi1 in tumorigenesis. Bmi1 is overexpressed in a variety of human cancers and it...

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“…Although further clinical evidence is needed, accumulating studies have suggested that MEL-18 acts as a tumor suppressor in several human tumors, including breast cancer (7)(8)(9)(10)(11). Our previous studies have also revealed that MEL-18 loss facilitates stem cell activity, cell growth, angiogenesis, and epithelial-mesenchymal transition (EMT) in breast cancer (12)(13)(14)(15), implying an association of MEL-18 loss with an aggressive phenotype.…”

Section: Introductionmentioning

confidence: 97%

MEL-18 loss mediates estrogen receptor–α downregulation and hormone independence

Lee¹,

Won²,

Park³

et al. 2015

J. Clin. Invest.

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BMI1 and Mel-18 oppositely regulate carcinogenesis and progression of gastric cancer

Cited by 83 publications

References 35 publications

Polycomb preferentially targets stalled promoters of coding and noncoding transcripts

Polycomb preferentially targets stalled promoters of coding and noncoding transcripts

Plasma Bmi1 mRNA as a potential prognostic biomarker for distant metastasis in colorectal cancer patients

MEL-18 loss mediates estrogen receptor–α downregulation and hormone independence

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