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MicroRNA profiling of benign and malignant adrenocortical tumors reveals potential biomarkers of recurrence

ABSTRACT: MicroRNAs are small, non-coding RNAs that regulate gene expression at post-transcriptional levels. There is increasing evidence to suggest that miRNAs could be useful in cancer diagnosis, prognosis, and therapy. The aim of our study was to identify miRNAs predictors of poor prognosis in adrenocortical cancer. miRNA microarray expression profiling was performed on a cohort of 6 adenomas, 6 non-recurrent carcinomas (Carc_B) and 6 recurrent carcinomas (Carc_A). We identified several miRNAs that were differentially expressed between adenomas and carcinomas as well as between Carc_A and Carc_B. We found that the best discriminatory miRNAs between carcinomas and adenomas were miR-195 and miR-335 which were down-regulated in carcinomas. MiR-139-5p was the most powerful discriminatory miRNA between Carc_A and Carc_B subtypes with consistent up-regulation in the recurrent carcinoma subgroup (Carc_A). Target prediction analysis showed that predicted targets of these miRNAs could be involved in biological processes and pathways that enhance tumor progression. Our data suggest that adrenocortical cancer cells progressively switch from a high miR-195 and miR-335 status to a low miR-195 and miR-335 phenotype. MiR-139-5P is a potential prognostic biomarker of recurrent adrenocortical carcinomas.

ORGANISM(S): Mus musculus Rattus norvegicus Human gammaherpesvirus 8 synthetic construct JC polyomavirus Homo sapiens Human immunodeficiency virus 1 human gammaherpesvirus 4 Murid gammaherpesvirus 4 Human betaherpesvirus 5 Murid betaherpesvirus 1

PROVIDER: GSE43279 | GEO | 2013/06/30

SECONDARY ACCESSION(S): PRJNA185263

REPOSITORIES: GEO

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MicroRNA profiling of benign and malignant adrenocortical tumors reveals potential biomarkers of recurrence

Project description:MicroRNAs are small, non-coding RNAs that regulate gene expression at post-transcriptional levels. There is increasing evidence to suggest that miRNAs could be useful in cancer diagnosis, prognosis, and therapy. The aim of our study was to identify miRNAs predictors of poor prognosis in adrenocortical cancer. miRNA microarray expression profiling was performed on a cohort of 6 adenomas, 6 non-recurrent carcinomas (Carc_B) and 6 recurrent carcinomas (Carc_A). We identified several miRNAs that were differentially expressed between adenomas and carcinomas as well as between Carc_A and Carc_B. We found that the best discriminatory miRNAs between carcinomas and adenomas were miR-195 and miR-335 which were down-regulated in carcinomas. MiR-139-5p was the most powerful discriminatory miRNA between Carc_A and Carc_B subtypes with consistent up-regulation in the recurrent carcinoma subgroup (Carc_A). Target prediction analysis showed that predicted targets of these miRNAs could be involved in biological processes and pathways that enhance tumor progression. Our data suggest that adrenocortical cancer cells progressively switch from a high miR-195 and miR-335 status to a low miR-195 and miR-335 phenotype. MiR-139-5P is a potential prognostic biomarker of recurrent adrenocortical carcinomas. Six tumor samples from patients with adrenocortical adenomas (Adenoma_1 to Adenoma_6), six tumor samples from patients with aggressive carcinomas (Carc_A1 to Carc_A6) and six tumor samples from patients with non-aggressive carcinoma (Carc_B1 to Carc_B6) were used to prepare total RNA for microarray analysis using MiRXploreTM Microarrays. miRXplore Universal Reference was used as control. One tumor sample was used per array.

2013-06-30 | E-GEOD-43279 | biostudies-arrayexpress

Deregulated miRNAs in adrenocortical tumors

Project description:We performed miRNA expression profiling in a series of adrenocortical carcinomas, adrenocortical adenomas and normal adreno cortex using a microarray approach. Significant differentially expressed miRNAs among groups were identified using SAM analysis. Agilent microarray platform containing 903 miRNAs was used to determine miRNA expression profiles in 4 normal cortices, 26 adenomas and 22 adrenocortical carcinomas. SAM analysis was adopted to identify significant differentially expressed miRNAs between groups. SAM survival analysis was used to determine the association between miRNA expression and survival among carcinoma cases. The expression levels of candidate prognostic miRNAs were evaluated using qRT-PCR in the same cohort of adrenocortical carcinomas and association with survival was evaluated using Kaplan Meier curves and log rank tests.

2011-06-01 | E-GEOD-22816 | biostudies-arrayexpress

Deregulated miRNAs in adrenocortical tumors

2011-06-01 | GSE22816 | GEO

Genome wide DNA Methylation analysis of benign and malignant adrenocortical tumors

Project description:Genome wide DNA methylation profiling of normal adrenocortical tissue, adrenocortical adenomas and adrenocortical carcinomas. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles. Samples included 6 normal adrenocortical tissue samples, 27 adenomas and 15 carcinomas.

2012-09-01 | GSE36353 | GEO

Genome wide DNA Methylation analysis of benign and malignant adrenocortical tumors

2012-09-01 | E-GEOD-36353 | biostudies-arrayexpress

Microarray profiling analysis of miRNAs expression in relapse melanoma post-radiation

Project description:Recent development of integrative therapy against melanoma combines surgery, radiotherapy, targeted therapy, and immunotherapy; however, the clinical outcomes of advanced stage and recurrent melanoma are poor. As a skin cancer, melanoma is generally resistant to radiotherapy. Hence, there is an urgent need for evaluation of the mechanisms of radioresistance. The present study identified miR-335 as one of the differential expression of miRNAs in recurrent melanoma biopsies post-radiotherapy. The expression of miR-335 declined in melanoma tissues compared to the adjacent tissues. Moreover, miR-335 expression correlated with advanced stages of melanoma negatively. Consistent with the prediction of STARBASE and miRDB database, miR-335 targeted ROCK1 via binding with 3’-UTR of ROCK1 directly, resulting in attenuation of proliferation, migration and radioresistance of melanoma cells. The authors validated that overexpression of miR-335 enhanced X-ray-induced tumor regression by B16 mouse models. Briefly, the present findings gained insights into miR-335/ROCK1-mediated radiosensitivity and provided a promising therapeutic strategy for improving radiotherapy against melanoma. miRNAs profiling by array

2020-02-13 | GSE143777 | GEO

Micro-RNA sequencing from 78 adrenocortical carcinomas

Project description:Micro-RNA sequencing of adrenocortical tumors and normal adrenal samples. miRNA sequencing of 45 adrenocortical carcinomas (ACC), 30 adrenocortical adenomas (ACA) and 3 normal adrenal samples.

2014-04-29 | E-GEOD-49279 | biostudies-arrayexpress

Characterization of differential gene expression in adrenocortical tumors harbouring β-catenin (CTNNB1) mutations.

Project description:Mutations of β-catenin gene (CTNNB1) are frequent in adrenocortical adenomas (AA) and carcinomas (ACC). However, the target genes of CTNNB1 have not yet been identified in adrenocortical tumors. Our objective was to identify genes de-regulated in adrenocortical tumors harbouring CTNNB1 genetic alterations.

2011-04-09 | GSE28476 | GEO

Beta-catenin status effects in human adrenocortical carcinomas (33), adenomas (22), and normal adrenal cortex (10)

Project description:We scored adrenocortical carcinomas and adenomas for abnormal beta-catenin staining, and sequenced the beta-catenin gene in some samples. We compared adrenocortincal carcinomas with and without abnormal beta-catenin staining and found many significant expression differences and significant results from enrichment testing. A similar comparison in the adenomas gave relatively few differences, and they did not correlate to differences found for the carcinomas. Abnormal beta-catenin staining was associated with mitotic rate and poorer patient survival in the carcinomas. In a second independent data set (given in a supplement) we again found beta-catenin associated with poor survival. The array data given is the same as GEO series GSE10927, with additional characteristics about beta-catenin, and new patient followup data. The analysis shown in a supplementary Excel file is also new. Human samples of 33 adrenocortical carcinomas, 22 adrenocortical adenomas, and 10 normal adrenal cortex samples, each from a different patient, had mRNA assays performed using Affymetrix HG_U133_plus_2 arrays, with 54675 probe-sets. 23 of the carcinomas were used in survival analysis. 27 additional samples without array data were also used in a survival analysis.

2011-11-02 | E-GEOD-33371 | biostudies-arrayexpress

Proteomic analysis upon miR195/497 replacement reveals potential chemo sensitizing candidates for colorectal cancer

Project description:Patients with advanced colorectal cancer (CRC) are commonly treated with systemic combination therapy but suffer eventually from drug resistance. MicroRNAs (miRNAs) are suggested to play a role in treatment resistance of CRC. We studied whether restoring downregulated miR-195-5p and 497-5p sensitize CRC cells to currently used chemotherapeutics 5-fluorouracil, oxaliplatin and irinotecan. Sensitivity to 5-FU, oxaliplatin and irinotecan before and after transfection with miR-195-5p and miR-497-5p mimics was analyzed in CRC cell lines HCT116, RKO, DLD-1 and SW480. Mass spectrometry based proteomic analysis of transfected and wild-type cells was used to identify targets involved in sensitivity to chemotherapy. Proteomic analysis revealed 181 proteins with significantly altered expression after transfection with miR-195-5p mimic in HCT116 and RKO, including 118 downregulated and 63 upregulated proteins. After transfection with miR-497-5p mimic, 130 proteins were significantly downregulated and 102 were upregulated in HCT116 and RKO (P<0.05 and FC<-3 or FC>3). CHUK and LUZP1 were coinciding downregulated proteins in sensitized CRC cells after transfection with either mimic. Resistance mechanisms of these two proteins may be related to nuclear factor kappa-B signaling and G1 cell cycle arrest, respectively. Restoring miR-195-5p and miR-497-5p expression enhanced sensitivity to chemotherapy, mainly oxaliplatin, in CRC cells and could be a promising treatment strategy for patients with mCRC. Proteomics revealed potential targets of these miRNAs involved in sensitivity to chemotherapy.

2019-09-27 | PXD015369 | Pride

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