Genome-wide expression profiling in colorectal cancer focusing on lncRNAs in the adenoma-carcinoma transition

Autor: Alexandra Kalmár, Zsófia Brigitta Nagy, Orsolya Galamb, István Csabai, András Bodor, Barnabás Wichmann, Gábor Valcz, Barbara Kinga Barták, Zsolt Tulassay, Peter Igaz, Béla Molnár
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: BMC Cancer, Vol 19, Iss 1, Pp 1-16 (2019)
Druh dokumentu: article
ISSN: 1471-2407
DOI: 10.1186/s12885-019-6180-5
Popis: Abstract 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
Databáze: Directory of Open Access Journals
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