Role of micro<scp>RNA</scp>s Located on Chromosome Arm 10q in Malignant Gliomas

Wolter, Marietta; Werner, Thomas; Malzkorn, Bastian; Reifenberger, Guido

doi:10.1111/bpa.12294

Cited by 30 publications

(21 citation statements)

References 52 publications

(75 reference statements)

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“…For example, miR-146a-5P (Log2 =1.88) has a critical role in the process of AIPC prostate cancer cells apoptosis through regulation of ROCK/Caspase 3 pathway, and caspase 3 activity was stimulated by miR-146a overexpression [ 23 ]. Overexpression of miR-146b-5P (log2 =1.43) in glioma cell lines reduced cell proliferation and increased caspase-3/7 activity [ 24 ]. These results are consistent with the aforementioned protein analysis in this research.…”

Section: Resultsmentioning

confidence: 99%

Steviol, a natural product inhibits proliferation of the gastrointestinal cancer cells intensively

et al. 2018

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New anticancer agents with lower toxicity have been always urged because of drug resistance associated with overused chemotherapy agents. In this study, steviol, a colonic metabolite of natural sweetener and also a component in leaves of stevia rebaudiana bertoni, was found to possess intensive anticancer activity on the human gastrointestinal cancer cells. Steviol inhibited six human gastrointestinal cancer cells intensively as 5-fluorouracil did at 100 μg/mL. The inhibition mechanism follows mitochondrial apoptotic pathway that was evidenced by increase of Bax/Bcl-2 ratio, activation of p21 and p53; and caspase 3-independent mechanism was also involved. These results are consistent with the miRNA expression analysis. The most regulated miRNAs in the steviol treated gastrointestinal cancer cells were miR-203a-3p (log2 =1.32) and miR-6088 (log2 =-2.54) in HCT-116, miR-1268b (log2 =19.85) and miR-23c (log2 =-2.05) in MKN-45. In view of the metabolic characteristics of steviol and its cytotoxicity on the cancer cells, steviol could be a chemotherapy agent potentially for cancer treatment.

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Section: Resultsmentioning

confidence: 99%

Steviol, a natural product inhibits proliferation of the gastrointestinal cancer cells intensively

et al. 2018

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“…This miRNA was also previously described as overexpressed in PTC [ 7 , 14 , 15 ]. Contrarily, the hypermethylation and down-expression of MIR146B were reported in diffuse and anaplastic astrocytomas, gliomas, and breast cancer being the 5-AZA-dC treatment capable to induce the MIR146B expression [ 23 , 24 ]. Taken together, these findings give evidences of the regulatory role of MIR146B in different tumor types, being able to act as tumor suppressor or oncomiR, depending on the context of altered regulatory pathways in each tumor type [ 25 – 28 ].…”

Section: Discussionmentioning

confidence: 99%

Loss of DNA methylation is related to increased expression of miR-21 and miR-146b in papillary thyroid carcinoma

et al. 2018

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BackgroundDNA methylation in miRNA genes has been reported as a mechanism that may cause dysregulation of mature miRNAs and consequently impact the gene expression. This mechanism is largely unstudied in papillary thyroid carcinomas (PTC).MethodsTo identify differentially methylated miRNA-encoding genes, we performed global methylation analysis (Illumina 450 K), integrative analysis (TCGA database), data confirmation (pyrosequencing and RT-qPCR), and functional assays.ResultsMethylation analysis revealed 27 differentially methylated miRNA genes. The integrative analyses pointed out miR-21 and miR-146b as potentially regulated by methylation (hypomethylation and increased expression). DNA methylation and expression patterns of miR-21 and miR-146b were confirmed as altered, as well as seven of 452 mRNAs targets were down-expressed. The combined methylation and expression levels of miR-21 and miR-146b showed potential to discriminate malignant from benign lesions (91–96% sensitivity and 96–97% specificity). An increased expression of miR-146b due to methylation loss was detected in the TPC1 cell line. The miRNA mimic transfection highlighted putative target mRNAs.ConclusionsThe increased expression of miR-21 and miR-146b due to loss of DNA methylation in PTC resulted in the disruption of the transcription machinery and biological pathways. These miRNAs are potential diagnostic biomarkers, and these findings provide support for future development of targeted therapies.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0579-8) contains supplementary material, which is available to authorized users.

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“…A possible mechanism for the downregulation of hsa-miR-107 could be its localization on the long arm of chromosome 10 (10q), which is lost in up to 80% of glioblastomas alongside other tumor suppressors e.g. PTEN [ 35 , 52 ]. Alternatively, downregulation could be explained by epigenetic silencing of the hsa-miR-107 promoter as seen in pancreatic cancer [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

A 4-miRNA signature to predict survival in glioblastomas

et al. 2017

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Glioblastomas are among the most lethal cancers; however, recent advances in survival have increased the need for better prognostic markers. microRNAs (miRNAs) hold great prognostic potential being deregulated in glioblastomas and highly stable in stored tissue specimens. Moreover, miRNAs control multiple genes representing an additional level of gene regulation possibly more prognostically powerful than a single gene. The aim of the study was to identify a novel miRNA signature with the ability to separate patients into prognostic subgroups. Samples from 40 glioblastoma patients were included retrospectively; patients were comparable on all clinical aspects except overall survival enabling patients to be categorized as short-term or long-term survivors based on median survival. A miRNome screening was employed, and a prognostic profile was developed using leave-one-out cross-validation. We found that expression patterns of miRNAs; particularly the four miRNAs: hsa-miR-107_st, hsa-miR-548x_st, hsa-miR-3125_st and hsa-miR-331-3p_st could determine short- and long-term survival with a predicted accuracy of 78%. Heatmap dendrograms dichotomized glioblastomas into prognostic subgroups with a significant association to survival in univariate (HR 8.50; 95% CI 3.06–23.62; p<0.001) and multivariate analysis (HR 9.84; 95% CI 2.93–33.06; p<0.001). Similar tendency was seen in The Cancer Genome Atlas (TCGA) using a 2-miRNA signature of miR-107 and miR-331 (miR sum score), which were the only miRNAs available in TCGA. In TCGA, patients with O6-methylguanine-DNA-methyltransferase (MGMT) unmethylated tumors and low miR sum score had the shortest survival. Adjusting for age and MGMT status, low miR sum score was associated with a poorer prognosis (HR 0.66; 95% CI 0.45–0.97; p = 0.033). A Kyoto Encyclopedia of Genes and Genomes analysis predicted the identified miRNAs to regulate genes involved in cell cycle regulation and survival. In conclusion, the biology of miRNAs is complex, but the identified 4-miRNA expression pattern could comprise promising biomarkers in glioblastoma stratifying patients into short- and long-term survivors.

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Role of microRNAs Located on Chromosome Arm 10q in Malignant Gliomas

Cited by 30 publications

References 52 publications

Steviol, a natural product inhibits proliferation of the gastrointestinal cancer cells intensively

Steviol, a natural product inhibits proliferation of the gastrointestinal cancer cells intensively

Loss of DNA methylation is related to increased expression of miR-21 and miR-146b in papillary thyroid carcinoma

A 4-miRNA signature to predict survival in glioblastomas

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