Polymorphisms at the microRNA binding-site of the stem cell marker gene<i>CD133</i>modify susceptibility to and survival of gastric cancer

Wang, Qiming; Liu, Hongliang; Xiong, Huihua; Liu, Zhensheng; Wang, Li E.; Qian, Ji; Muddasani, Ramya; Lu, Victoria; Tan, Dongfeng; Ajani, Jaffer A.; Wei, Qingyi

doi:10.1002/mc.22113

Cited by 20 publications

(11 citation statements)

References 39 publications

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“…Luciferase report assay showed that the rs6976789 variant T allele influenced the binding ability of miR-148a. Similar research have been done in GC [33,34,35]. …”

Section: Discussionsupporting

confidence: 60%

Genetic Variations and Gastric Cancer

Yu¹,

Chen²

2015

Gastrointest Tumors

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Background: Gastric cancer (GC) has an apparent hereditary component. However, in a large fraction of gastric cases, no known genetic syndrome or family history can be identified, suggesting the presence of ‘missing heritability' in GC etiology. Genome-wide association studies (GWAS) and traditional candidate gene studies have both led to the identification of multiple replicable common genetic variants associated with GC risk. Summary: We summarize the genetic variants associated with GC risk identified up to date. Achievements derived from translational cancer research including the following aspects: (a) contribution to the our understanding of gastric tumorigenesis, (b) guidance to individualized treatment and (c) prediction of patient prognosis. We also prospect future research direction such as post-GWAS analyses and rare variants studies. Key Message: Many genetic variants were found through GWAS or candidate gene studies, and interpreting their underlying mechanisms will help us translate risk profiles generated from these variations into use in the clinical setting for targeted screening and treatment. Practical Implications: Investigation of the potential use of genetic variations as prognostic and predictive markers is a developing field. Many people could benefit from a better understanding of genetic polymorphisms to potentially identify a priori individuals who might have the best chance of survival and therefore derive most clinical benefit from treatment. Outcomes of particular scientific interest for molecular epidemiologic studies should include overall survival, recurrence- and progression-free survival, response to treatment, and early and late toxicities stemming from chemotherapy and radiation.

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“…Luciferase report assay showed that the rs6976789 variant T allele influenced the binding ability of miR-148a. Similar research have been done in GC [33,34,35]. …”

Section: Discussionsupporting

confidence: 60%

Genetic Variations and Gastric Cancer

Yu¹,

Chen²

2015

Gastrointest Tumors

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“…One key molecular characteristic of CSCs is their capability of extensive proliferation and clone formation in suspension culture [ 9 ], and tumor sphere-forming assays have been widely applied to identify potential CSC populations [ 10 ]. There were some reports suggesting CD133, CD44, EPCAM and CD90 as molecular markers of CSCs [ 11 – 14 ], and CSCs can also be isolated using flow cytometry according to the expression of these specific cell surface markers, such as CD133 and CD44 [ 15 , 16 ]. However, it is still quite challenging and time-consuming to identify CSC cells by simply using these markers.…”

Section: Introductionmentioning

confidence: 99%

Doxycycline Induces Apoptosis and Inhibits Proliferation and Invasion of Human Cervical Carcinoma Stem Cells

Yang

Zhang

et al. 2015

PLoS ONE

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BackgroundCancer stem cells (CSCs) are proposed to be responsible for high recurrence rate in cervical carcinoma. Reagents that can suppress the proliferation and differentiation of CSCs would provide new opportunities to fight against tumor recurrence. Doxycycline has been reported as a potential anti-cancer compound. However, few studies investigated its inhibitory effect against cervical cancer stem cells.MethodsHeLa cells were cultured in cancer stem cell conditional media in a poly-hema-treated dish. In this non-adhesive culture system, HeLa cells were treated with cisplatin until some cells survived and formed spheroids, which were then collected and injected into the immunodeficient mice. Cisplatin was administered every three days for five times. The tumor xenografts with CSC enrichment were cultured in cancer stem cell specific medium again to form tumorsphere, which we called HeLa-CSCs. Expression of cancer stem cell markers in HeLa-CSCs was measured by flow cytometry and qPCR. HeLa-CSCs were then treated with doxycycline. Proliferation and differentiation rates were determined by the size of spheres formed in vitro and tumor formed in vivo.ResultsWe developed a new strategy to selectively enrich CSCs from human cervical carcinoma cell line HeLa, and these HeLa-CSCs are CD133+/CD49f+ cell populations with significantly enhanced expression of stem cell markers. When these HeLa-CSCs were treated with doxycycline, the colony formation, proliferation, migration and invasion, and differentiation were all suppressed. Meanwhile, stem cell markers SOX-2, OCT-4, NANOG, NOTCH and BMI-1 decreased in doxycycline treated cells, so as the surface markers CD133 and CD49f. Furthermore, proliferation markers Ki67 and PCNA were also decreased by doxycycline treatment in the in vivo xenograft mouse model.ConclusionsCancer stem cells are enriched from sphere-forming and chemoresistant HeLa-derived tumor xenografts in immunodeficient mice. Doxycycline inhibits proliferation, invasion, and differentiation, and also induces apoptosis of these HeLa-CSCs in vitro and in vivo.

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“…There is also a growing body of information pertaining to various genetic polymorphisms which may confer risk for worsening gastric cancer phenotype, differential responses to treatment and differences in survival. [23][24][25]64,65 This type of molecular information will allow for more selective testing of therapies in subgroups of patients with gastric cancer and may lead to more accurate survival predictions in the future.…”

Section: Molecular Markersmentioning

confidence: 99%