| Experiment ID | EXP00256 |
| Reference | Title: Impact of microRNAs on regulatory networks and pathways in human colorectalcarcinogenesis and development of metastasis. Author: Pizzini S, Bisognin A, Mandruzzato S, Biasiolo M, Facciolli A, Perilli L,Rossi E, Esposito G, Rugge M, Pilati P, Mocellin S, Nitti D, Bortoluzzi S,Zanovello P. Journal: BMC Genomics. 2013 Aug 29;14:589. doi: 10.1186/1471-2164-14-589. Abstract: BACKGROUND: Qualitative alterations or abnormal expression of microRNAs (miRNAs) in colon cancer have mainly been demonstrated in primary tumors. Poorlyoverlapping sets of oncomiRs, tumor suppressor miRNAs and metastamiRs have beenlinked with distinct stages in the progression of colorectal cancer. To identify changes in both miRNA and gene expression levels among normal colon mucosa,primary tumor and liver metastasis samples, and to classify miRNAs intofunctional networks, in this work miRNA and gene expression profiles in 158samples from 46 patients were analysed.RESULTS: Most changes in miRNA and gene expression levels had already manifested in the primary tumors while these levels were almost stably maintained in thesubsequent primary tumor-to-metastasis transition. In addition, comparing normal tissue, tumor and metastasis, we did not observe general impairment or any risein miRNA biogenesis. While only few mRNAs were found to be differentiallyexpressed between primary colorectal carcinoma and liver metastases, miRNAexpression profiles can classify primary tumors and metastases well, includingdifferential expression of miR-10b, miR-210 and miR-708. Of 82 miRNAs that weremodulated during tumor progression, 22 were involved in EMT. qRT-PCR confirmedthe down-regulation of miR-150 and miR-10b in both primary tumor and metastasiscompared to normal mucosa and of miR-146a in metastases compared to primarytumor. The upregulation of miR-201 in metastasis compared both with normal andprimary tumour was also confirmed. A preliminary survival analysis consideringdifferentially expressed miRNAs suggested a possible link between miR-10bexpression in metastasis and patient survival. By integrating miRNA and targetgene expression data, we identified a combination of interconnected miRNAs, whichare organized into sub-networks, including several regulatory relationships with differentially expressed genes. Key regulatory interactions were validatedexperimentally. Specific mixed circuits involving miRNAs and transcriptionfactors were identified and deserve further investigation. The suppressoractivity of miR-182 on ENTPD5 gene was identified for the first time andconfirmed in an independent set of samples.CONCLUSIONS: Using a large dataset of CRC miRNA and gene expression profiles, we describe the interplay of miRNA groups in regulating gene expression, which inturn affects modulated pathways that are important for tumor development. PMID: 23987127 |
| Expressiion Profile | Description: Impact of miRNAs modulation on regulatory networks and pathways involved in colon cancer and metastasis development Organism: Homo sapiens GEO ID: GSE35834 Platform: GPL8786 Number of samples: 158 |
| Design and Sample | Cancer Type: colon cancer Cancer SubType: N/D Cell Line: N/D Experimental Design: high grade vs low grade Case Sample: colon cancer grade 3 Control Sample: colon cancer grade 1 Num of Case: 27 Num of Control: 4 Quantification Software: Limma Num of miRNAs: 597 |
| Identification | Num of Up: 0 Num of Down: 5 |