Dataset Information

MicroRNA expression profiling in the colorectal normal-adenoma-carcinoma transition.

ABSTRACT: Colorectal adenoma is a major precursor to colorectal cancer. Investigating the alteration of microRNA (miRNA/miR) expression during the progression from normal colorectal tissue to adenoma, and finally to colorectal carcinoma may aid our understanding of the biological mechanisms of colorectal tumorigenesis. In the present study, the miRNA expression profiles of normal colorectal tissue, adenoma and colorectal carcinoma from 6 patients were evaluated using miRNA-sequencing. A total of 334 miRNAs were identified as differentially expressed. It was revealed that 34 miRNAs were upregulated in all 6 patients, including miR-135b-5p, miR-18a-5p and miR-29b-3p, and 28 miRNAs were downregulated, including miR-1-3p, miR-338-3p and miR-218-5p. Using bioinformatic analysis, the potential target genes of these 62 miRNAs were predicted and found to be enriched in 'transcription, DNA-dependent (GO:0006351)', 'signal transduction (GO:0007165)', 'small molecule metabolic process (GO:0044281)' 'PI3K/AKT signaling pathway (path ID:04151)' and 'MAPK signaling pathway (path ID:04010)'. The miRNA expression profiles identified in the present study may extend our understanding of the molecular mechanisms underlying colorectal tumorigenesis and promote novel perspectives for prevention, diagnosis and treatment.

SUBMITTER: Li J

PROVIDER: S-EPMC6607403 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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MicroRNA expression profiling in the colorectal normal-adenoma-carcinoma transition.

Li Jian J Zhong Yunshi Y Cai Shilun S Zhou Pinghong P Yao Liqing L

Oncology letters 20190610 2

Colorectal adenoma is a major precursor to colorectal cancer. Investigating the alteration of microRNA (miRNA/miR) expression during the progression from normal colorectal tissue to adenoma, and finally to colorectal carcinoma may aid our understanding of the biological mechanisms of colorectal tumorigenesis. In the present study, the miRNA expression profiles of normal colorectal tissue, adenoma and colorectal carcinoma from 6 patients were evaluated using miRNA-sequencing. A total of 334 miRNA ...[more]

PMID: 31423272

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Project description:BACKGROUND:Long non-coding RNAs (lncRNAs) play a fundamental role in colorectal cancer (CRC) development, however, lncRNA expression profiles in CRC and its precancerous stages remain to be explored. We aimed to study whole genomic lncRNA expression patterns in colorectal adenoma-carcinoma transition and to analyze the underlying functional interactions of aberrantly expressed lncRNAs. METHODS:LncRNA expression levels of colonic biopsy samples (20 CRCs, 20 adenomas (Ad), 20 healthy controls (N)) were analyzed with Human Transcriptome Array (HTA) 2.0. Expression of a subset of candidates was verified by qRT-PCR and in situ hybridization (ISH) analyses. Furthermore, in silico validation was performed on an independent HTA 2.0, on HGU133Plus 2.0 array data and on the TCGA COAD dataset. MiRNA targets of lncRNAs were predicted with miRCODE and lncBase v2 algorithms and miRNA expression was analyzed on miRNA3.0 Array data. MiRNA-mRNA target prediction was performed using miRWALK and c-Met protein levels were analyzed by immunohistochemistry. Comprehensive lncRNA-mRNA-miRNA co-expression pattern analysis was also performed. RESULTS:Based on our HTA results, a subset of literature-based CRC-associated lncRNAs showed remarkable expression changes already in precancerous colonic lesions. In both Ad vs. normal and CRC vs. normal comparisons 16 lncRNAs, including downregulated LINC02023, MEG8, AC092834.1, and upregulated CCAT1, CASC19 were identified showing differential expression during early carcinogenesis that persisted until CRC formation (FDR-adjusted p < 0.05). The intersection of CRC vs. N and CRC vs. Ad comparisons defines lncRNAs characteristic of malignancy in colonic tumors, where significant downregulation of LINC01752 and overexpression of UCA1 and PCAT1 were found. Two candidates with the greatest increase in expression in the adenoma-carcinoma transition were further confirmed by qRT-PCR (UCA1, CCAT1) and by ISH (UCA1). In line with aberrant expression of certain lncRNAs in tumors, the expression of miRNA and mRNA targets showed systematic alterations. For example, UCA1 upregulation in CRC samples occurred in parallel with hsa-miR-1 downregulation, accompanied by c-Met target mRNA overexpression (p < 0.05). CONCLUSION:The defined lncRNA sets may have a regulatory role in the colorectal adenoma-carcinoma transition. A subset of CRC-associated lncRNAs showed significantly differential expression in precancerous samples, raising the possibility of developing adenoma-specific markers for early detection of colonic lesions.

Project description:BACKGROUND:Circulating microRNAs (miRNAs) are emerging as promising biomarkers for cancer. The objective of the current study was to investigate the potential of circulating cell-free miRNAs as biomarkers for colorectal cancer (CRC) and its precursor lesion, colorectal adenoma. METHODS:The serum levels of 800 miRNAs were assessed in a discovery set of 21 patients with CRC, 19 patients with adenoma, and 21 healthy controls using the NanoString miRNA analysis platform. Significantly differentially expressed miRNAs were examined further in a validation cohort of 34 patients with CRC, 33 patients with adenoma, and 35 healthy controls using Fluidigm quantitative polymerase chain reaction assays. RESULTS:The ratios between the expression values of the differentially expressed miRNAs were computed. Three miRNA ratios (miR-17-5p/miR-135b, miR-92a-3p/miR135b, and miR-451a/miR-491-5p) were validated for discriminating patients with adenoma and those with CRC from the healthy control group, and 5 miRNA ratios (let-7b/miR-367-3p, miR-130a-3p/miR-409-3p, miR-148-3p/miR-27b, miR-148a-3p/miR-409-3p, and miR-21-5p/miR-367-3p) were validated for discriminating patients with CRC from those with adenoma and healthy controls. The area under the receiver operating characteristic curve values for the 3 miRNA ratios in discriminating patients with adenoma from healthy controls were 0.831 and 0.735, respectively, in the discovery and validation sets. The area under the receiver operating characteristic curve values for the 5 miRNA ratios in discriminating patients with CRC from those with adenoma were 0.797 and 0.732, respectively, in the discovery and validation sets. Pathway analysis revealed that target genes regulated by the miRNAs from the miRNA ratios were enriched mainly in metabolism-related and inflammation-related pathways. CONCLUSIONS:The data from the current study suggest that circulating miRNAs can distinguish patients with CRC and those with adenoma and may represent novel biomarkers for the early, noninvasive detection of CRC. Cancer 2018;124:785-96. © 2017 American Cancer Society.

Project description:To identify differences in gene expression profiles of infected cells between thyroid carcinoma (C), thyroid adenoma (A) and normal thyroid (N) epithelial cells, differentially expressed genes were identified using three pairwise comparisons with the GEO2R online tool. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to classify them at the functional level. The most significant cluster in the N vs. A pairwise comparison had four hub genes: Insulin-like growth factor 2, Von Willebrand factor (VWF), multimerin 1 (MMRN1) and complement factor D (CFD). In N vs. C, the most significant cluster had 19 genes: IGF2, early growth response 2, transcription factor 3, KIT proto‑oncogene receptor tyrosine kinase, SMAD family member 9, MLLT3 super elongation complex subunit, runt related transcription factor 1, CFD, actinin α 1, SWI/SNF related matrix associated actin dependent regulator of chromatin subfamily a member 4, JunD proto‑oncogene AP‑1 transcription factor subunit, serum response factor (SRF), FosB proto‑oncogene, AP‑1 transcription factor subunit, connective tissue growth factor (CTGF), SRC proto‑oncogene, non‑receptor tyrosine kinase, MMRN1, SRY‑box 9, early growth response 3 and ETS variant 4. In A vs. C, the most significant cluster had 14 genes: BCL2-like 1, galectin 3, MCL1 BCL2 family apoptosis regulator, DNA damage inducible transcript 3, BCL2 apoptosis regulator, CTGF, matrix metallopeptidase 7, early growth response 1, kinase insert domain receptor, TIMP metallopeptidase inhibitor 1, apolipoprotein E, VWF, cyclin D1 and placental growth factor. Histological evidence was presented to confirm the makeup of the hubs prior to logistic regression analysis to differentiate benign and malignant neoplasms. The results of the present study may aid in the search for novel potential biomarkers for the differential diagnosis, prognosis and development of drug targets of thyroid neoplasm.

Dataset Information

MicroRNA expression profiling in the colorectal normal-adenoma-carcinoma transition.

Publications

MicroRNA expression profiling in the colorectal normal-adenoma-carcinoma transition.

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