Loss of miR-204 Expression Enhances Glioma Migration and Stem Cell-like Phenotype

Ying, Zhe; Li, Yun; Wu, Jueheng; Zhu, Xun; Yang, Yi; Tian, Han; Li, Wei; Hu, Bo; Cheng, Shi Yuan; Li, Mengfeng

doi:10.1158/0008-5472.can-12-2895

Cited by 134 publications

(137 citation statements)

References 37 publications

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…It has an essential role in differentiation of neural stems cells and neural progenitor cells (34 ), and its downregulation promotes growth, invasiveness, and metastasis (35 ) by targeting laminin, gamma 1 (LAMC1), integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12) (ITGB1), cyclin-dependent kinase 6 (CDK6), and SRY (sex determining region Y)-box 9 (SOX9) (36 ). Similarly, miR-204 loss enhanced migration and stem cell phenotype in vivo (37 ). MiR-139 expression was shown to differ between different kidney cancer subtypes (38 ) and was also linked to metastasis and prognosis in ccRCC (39 ).…”

Section: Discussionmentioning

confidence: 93%

Integrative Bioinformatics Analysis Reveals New Prognostic Biomarkers of Clear Cell Renal Cell Carcinoma

et al. 2014

View full text Add to dashboard Cite

BACKGROUND The outcome of clear cell renal cell carcinoma (ccRCC) is still unpredictable. Even with new targeted therapies, the average progression-free survival is dismal. Markers for early detection and progression could improve disease outcome. METHODS To identify efficient and hitherto unrecognized pathogenic factors of the disease, we performed a uniquely comprehensive pathway analysis and built a gene interaction network based on large publicly available data sets assembled from 28 publications, comprising a 3-prong approach with high-throughput mRNA, microRNA, and protein expression profiles of 593 ccRCC and 389 normal kidney samples. We validated our results on 2 different data sets of 882 ccRCC and 152 normal tissues. Functional analyses were done by proliferation, migration, and invasion assays following siRNA (small interfering RNA) knockdown. RESULTS After integration of multilevel data, we identified aryl-hydrocarbon receptor (AHR), grainyhead-like-2 (GRHL2), and KIAA0101 as new pathogenic factors. GRHL2 expression was associated with higher chances for disease relapse and retained prognostic utility after controlling for grade and stage [hazard ratio (HR), 3.47, P = 0.012]. Patients with KIAA0101-positive expression suffered worse disease-free survival (HR, 3.64, P < 0.001), and in multivariate analysis KIAA0101 retained its independent prognostic significance. Survival analysis showed that GRHL2- and KIAA0101-positive patients had significantly lower disease-free survival (P = 0.002 and P < 0.001). We also found that KIAA0101 silencing decreased kidney cancer cell migration and invasion in vitro. CONCLUSIONS Using an integrative system biology approach, we identified 3 novel factors as potential biomarkers (AHR, GRHL2 and KIAA0101) involved in ccRCC pathogenesis and not linked to kidney cancer before.

show abstract

Section: Discussionmentioning

confidence: 93%

Integrative Bioinformatics Analysis Reveals New Prognostic Biomarkers of Clear Cell Renal Cell Carcinoma

et al. 2014

View full text Add to dashboard Cite

show abstract

“…First, miR‐204 targets EphB2 in glioma cells (Ying et al ., 2014) and regulates retinal axon guidance through Efnb3 (ephrin ligand) and EphB2 (receptor) during eye development in medaka (Conte et al ., 2014). We speculated that the age‐upregulated miR‐204 targets EphB2 mRNA and reduces EphB2 expression in aged hippocampus.…”

Section: Resultsmentioning

confidence: 99%

miR‐204 downregulates EphB2 in aging mouse hippocampal neurons

et al. 2016

View full text Add to dashboard Cite

SummaryHippocampal synaptic function and plasticity deteriorate with age, often resulting in learning and memory deficits. As MicroRNAs (miRNAs) are important regulators of neuronal protein expression, we examined whether miRNAs may contribute to this age‐associated decline in hippocampal function. We first compared the small RNA transcriptome of hippocampal tissues from young and old mice. Among 269 hippocampal miRNAs, 80 were differentially expressed (≥ twofold) among the age groups. We focused on 36 miRNAs upregulated in the old mice compared with those in the young mice. The potential targets of these 36 miRNAs included 11 critical Eph/Ephrin synaptic signaling components. The expression levels of several genes in the Eph/Ephrin pathway, including EphB2, were significantly downregulated in the aged hippocampus. EphB2 is a known regulator of synaptic plasticity in hippocampal neurons, in part by regulating the surface expression of the NMDA receptor NR1 subunit. We found that EphB2 is a direct target of miR‐204 among miRNAs that were upregulated with age. The transfection of primary hippocampal neurons with a miR‐204 mimic suppressed both EphB2 mRNA and protein expression and reduced the surface expression of NR1. Transfection of miR‐204 also decreased the total expression of NR1. miR‐204 induces senescence‐like phenotype in fully matured neurons as evidenced by an increase in p16‐positive cells. We suggest that aging is accompanied by the upregulation of miR‐204 in the hippocampus, which downregulates EphB2 and results in reduced surface and total NR1 expression. This mechanism may contribute to age‐associated decline in hippocampal synaptic plasticity and the related cognitive functions.

show abstract

“…We and other groups have shown that miR-204 is downregulated in multiple human cancers (7,(15)(16)(17)(18)(19)(20)(21)(22)(23). CpG methylation represents an important mechanism responsible for the inactivation of genes, including miRNAs.…”

Section: Discussionmentioning

confidence: 98%

“…TRPM3 and miR-204 share the same transcriptional regulatory motif and are derived from a single transcription unit (28,29). Previous study reported that the promoter CpG islands of TRPM3 were hypermethylated in glioma (21). We next sought to investigate whether the promoter hypermethylation also occurred in colorectal cancer and whether it was responsible for the downregulation of miR-204-5p.…”

Section: Downregulation Of Mir-204-5p Caused By Promoter Hypermethylamentioning

confidence: 99%

See 1 more Smart Citation

miR-204-5p Inhibits Proliferation and Invasion and Enhances Chemotherapeutic Sensitivity of Colorectal Cancer Cells by Downregulating RAB22A

Yin

Zhang

Wang

et al. 2014

Clinical Cancer Research

181

179

View full text Add to dashboard Cite

Purpose: miR-204-5p was found to be downregulated in colorectal cancer tissues in our preliminary microarray analyses. However, the function of miR-204-5p in colorectal cancer remains unknown. We therefore investigated the role, mechanism, and clinical significance of miR-204-5p in colorectal cancer development and progression.Experimental Design: We measured the expression of miR-204-5p and determined its correlation with patient prognoses. Ectopic expression in colorectal cancer cells, xenografts, and pulmonary metastasis models was used to evaluate the effects of miR-204-5p on proliferation, migration, and chemotherapy sensitivity. Luciferase assay and Western blotting were performed to validate the potential targets of miR-204-5p after the preliminary screening by a microarray analysis and computer-aided algorithms.Results: miR-204-5p is frequently downregulated in colorectal cancer tissues, and survival analysis showed that the downregulation of miR-204-5p in colorectal cancer was associated with poor prognoses. Ectopic miR-204-5p expression repressed colorectal cancer cell growth both in vitro and in vivo. Moreover, restoring miR-204-5p expression inhibited colorectal cancer migration and invasion and promoted tumor sensitivity to chemotherapy. Mechanistic investigations revealed that RAB22A, a member of the RAS oncogene family, is a direct functional target of miR-204-5p in colorectal cancer. Furthermore, RAB22A protein levels in colorectal cancer tissues were frequently increased and negatively associated with miR-204-5p levels and survival time.Conclusions: Our results demonstrate for the first time that miR-204-5p acts as a tumor suppressor in colorectal cancer through inhibiting RAB22A and reveal RAB22A to be a new oncogene and prognostic factor for colorectal cancer.

show abstract

Loss of miR-204 Expression Enhances Glioma Migration and Stem Cell-like Phenotype

Cited by 134 publications

References 37 publications

Integrative Bioinformatics Analysis Reveals New Prognostic Biomarkers of Clear Cell Renal Cell Carcinoma

Integrative Bioinformatics Analysis Reveals New Prognostic Biomarkers of Clear Cell Renal Cell Carcinoma

miR‐204 downregulates EphB2 in aging mouse hippocampal neurons

miR-204-5p Inhibits Proliferation and Invasion and Enhances Chemotherapeutic Sensitivity of Colorectal Cancer Cells by Downregulating RAB22A

Contact Info

Product

Resources

About