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A systematic approach to the metastatically relevant microRNA landscape

ABSTRACT: Identification of differentially expressed microRNAs in Colorectal Cancer Distant metastasis is the major determinant of patient outcome in colorectal cancer and microRNAs have emerged as an increasingly important class of molecules which can regulate several steps of the metastatic cascade. By systematically analysing the miR expression profiles of resected metastasis-, corresponding primary tumor- and normal tissues of colorectal cancer patients, we were able to delineate a miR-signature indicative of the metastatically critical microRNA landscape.

ORGANISM(S): Homo sapiens

PROVIDER: GSE54088 | GEO | 2014/01/16

SECONDARY ACCESSION(S): PRJNA235163

REPOSITORIES: GEO

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A systematic approach to the metastatically relevant microRNA landscape

Project description:Identification of differentially expressed microRNAs in Colorectal Cancer Distant metastasis is the major determinant of patient outcome in colorectal cancer and microRNAs have emerged as an increasingly important class of molecules which can regulate several steps of the metastatic cascade. By systematically analysing the miR expression profiles of resected metastasis-, corresponding primary tumor- and normal tissues of colorectal cancer patients, we were able to delineate a miR-signature indicative of the metastatically critical microRNA landscape. 9 colorectal cancer patients were profiled comprising 5 patients with tissues from the primary tumor, normal mucosa, secondary metastasis and the background tissue in which the metastasis ocurred. In the remaining 4 patients, one of these four tissue entitities is missing. One patient had two synchronous primary tumors, one in the colon and the other in the rectum.

2014-01-16 | E-GEOD-54088 | biostudies-arrayexpress

Systematic analysis of intronic microRNAs reveals cooperativity within the multi-component FTX locus to promote colon cancer development

Project description:Approximately half of all microRNAs reside within intronic regions and are often co-transcribed with their host genes. However, most studies on intronic microRNAs focus on individual microRNAs, and conversely most studies on protein-coding and non-coding genes frequently ignore any intron-derived microRNAs. We hypothesize that the individual components of such multi-genic loci may play cooperative or competing roles in driving disease progression, and that examining the combinatorial effect of these components would uncover deeper insights into their functional importance. To address this, we perform systematic analyses of intronic microRNA:host loci in colon cancer. We observe that the FTX locus, comprising of a long non-coding RNA FTX and multiple intronic microRNAs, is highly upregulated in cancer and demonstrate that cooperativity within this multi-component locus promotes cancer growth. In addition, we show that FTX interacts with DHX9 and DICER and delineate its novel roles in regulating A-to-I RNA editing and microRNA expression. These results show for the first time that a long non-coding RNA can regulate A-to-I RNA editing, further expanding the functional repertoire of long non-coding RNAs. We further demonstrate the inhibitory effects of intronic miR-374b and -545 on the tumor suppressors PTEN and RIG-I to enhance the proto-oncogenic PI3K-AKT signaling. Finally, we show that intronic miR-421 may exert an autoregulatory effect on miR-374b and -545. Taken together, our data unveil the intricate interplay between intronic microRNAs and their host transcripts in the modulation of key signaling pathways and disease progression, adding new perspectives to the functional landscape of multi-genic loci.

2021-01-05 | PXD021823 | Pride

Five microRNAs in serum are able to differentiate breast cancer patients from healthy individuals

Project description:Breast Cancer is the cancer with most incidence and mortality in women. microRNAs are emerging as novel prognosis/diagnostic tools. Our aim was to identify a serum microRNA signature useful to predict cancer development. We focused on studying the expression levels of 30 microRNAs in the serum of 96 breast cancer patients versus 92 control individuals. Bioinformatic studies provide a microRNA signature, designated as a predictor, based upon the expression levels of 5 microRNAs. Then, we tested the predictor in a group of 60 randomly chosen women. Lastly, a proteomic study unveiled the over-expression and down-regulation of proteins differently expressed in the serum of breast cancer patients versus that of control individuals. Twenty-six microRNAs differentiate cancer tissue from healthy tissue and 16 microRNAs differentiate the serum of cancer patients from that of the control group. The tissue expression of miR-99a-5p, mir-497-5p, miR-362, and miR-1274, and the serum levels of miR-141 correlated with patient survival. Moreover, the predictor consisting of mir-125b-5p, miR-29c-3p, mir-16-5p, miR-1260, and miR-451a was able to differentiate breast cancer patients from controls. The predictor was validated in 20 new cases of breast cancer patients and tested in 60 volunteer women, assigning 11 out of 60 women to the cancer group. An association of low levels of mir-16-5p with a high content of CD44 protein in serum was found. Circulating microRNAs in serum can represent biomarkers for cancer prediction. Their clinical relevance and use of the predictor here described might be of potential importance for breast cancer prediction.

2020-09-18 | PXD020795 | Pride

hepatic metastatic colorectal cancer gene expression array

Project description:The goal of this experiment was to build gene expression signature associated with long-term outcomes of patients with hepatic metastatic colorectal cancer. The samples were corrected from surgically resected liver metastasis and extracted RNA was subjected to Illumina expression gene chip analysis.

2014-01-14 | E-MTAB-1951 | biostudies-arrayexpress

Gene expression signature and the prediction of liver metastasis in colorectal cancer by DNA microarray

Project description:Samples were taken from colorectal cancers in surgically resected specimens in 189 colorectal cancer patients. The expression profiles were determined using Affymetrix Human Genome U133 Plus 2.0 arrays. Comparison between the sample groups allow to identify a set of discriminating genes that can be used for molecular markers for predicting liver metastasis. Keywords: repeat

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Gene expression signature and the prediction of recurrence in stage III colorectal cancer by DNA microarray

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2010-08-31 | E-GEOD-4526 | biostudies-arrayexpress

MicroRNA expression profile between human colorectal cancer SW480 and SW620 cell line

Project description:Two isogenic human colorectal cancer cell lines (primary SW480 cell line and its lymph node metastatic variant SW620 cell line),as an in vitro metastatic model. We have demonstrated that SW620 cell line possesses high metastasis potential and SW480 cell linepossesses low metastatic potential. We want to compare the whole cell microRNAs profiles of two isogenic colorectal cancer cell lines (SW480 and SW620 cell line), to gain an insight into the molecular events of colon cancer metastasis.

2016-08-01 | E-GEOD-72412 | biostudies-arrayexpress

Homo sapiens

Project description:colorectal cancer metastasis

| PRJNA393626 | ENA

A microRNA/circle RNA axis promotes metastasis through CDR1-mediated anoikis-resistance

Project description:Lung cancer is an intrinsically highly metastatic disease and the leading cause of cancer-related deaths worldwide. Although discovery of molecular aberrations in lung adenocarcinomas has led to development of effective targeted therapies, corresponding “drivers” in lung squamous carcinomas (LUSC) have not materialized. Extensive molecular profiling has revealed LUSC tumors have non-recurrent somatic mutations and are largely driven by copy number alterations. Because microRNAs (miRs) play increasingly important roles in regulating metastasis-relevant pathways, we evaluated whether miRs can regulate LUSC progression. By integrating bioinformatics of the Cancer Genome Atlas (TCGA) with novel, highly metastatic LUSC models, we found that miR-671-5p is a key inhibitor of LUSC metastasis. Surprisingly, miR-671-5p regulates LUSC metastasis by inhibiting a circular RNA (circRNA), CDR1as. Although the putative function of CDR1as is through miR-7 sponging, we found miR-671-5p more potently silences an axis of CDR1as and its anti-sense transcript, cerebellar degeneration related antigen 1 (CDR1). To our knowledge, no function of CDR1 has ever been described. We found loss of CDR1as and CDR1 significantly inhibited LUSC metastases. Intriguingly, CDR1 was strongly associated with an epithelial-mesenchymal transition (EMT) program in LUSC tumors, and was sufficient to promote metastases, increased migration and substrate-independent survival, known as anoikis-resistance. CDR1, which directly interacts with AP1 and COPI subunits, no longer promoted migration and anoikis-resistance upon blockade of Golgi trafficking. Our findings reveal a miR/circRNA axis that regulates LUSC metastases through an enigmatic protein, CDR1.

2021-09-08 | PXD012286 | Pride

Expression alterations of miRNAs in SW620, HCT116, HUVEC cells exposed to 200 μg/mL PEP06 for 24 h relative to control cells without drugs.

Project description:Using the highly sensitive miRNA array, we screened the abundance of 2043 microRNAs in 2 colorectal cancer cell lines SW620 and HCT116, as well as HUVEC post treatment of PEP06. Among the 2043 microRNAs, 23 were found to be aberrantly expressed with statistical significances between the control and the PEP06 treated group. In the validating study with real-time PCR and Northern blot, miR-146b-5p was revealed significantly regulated by treatment of PEP06 in vivo and in vitro. We next explored the functions of miR-146b-5p in the EMT process in colorectal cancer. Our findings gave new insights in disclosing the mechanism by which PEP06 induces colorectal cancer inhibition.

2018-03-07 | GSE111493 | GEO

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