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MicroRNA profiling differentiates colorectal cancer according to KRAS status
Author(s) -
Mosakhani Neda,
Sarhadi Virinder Kaur,
Borze Ioana,
KarjalainenLindsberg MarjaLiisa,
Sundström Jari,
Ristamäki Raija,
Österlund Pia,
Knuutila Sakari
Publication year - 2012
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20925
Subject(s) - kras , microrna , colorectal cancer , biology , cancer research , gene expression profiling , mutant , real time polymerase chain reaction , cancer , bioinformatics , gene , gene expression , genetics
Abstract Recent studies have shown the important role of microRNAs (miRNAs) in a variety of biological processes, and in its ability to distinguish tumors according to their prognostic and predictive properties. To identify miRNA signatures associated with colorectal carcinoma (CRC) and with KRAS status, we studied, using Agilent's miRNA microarrays, miRNA expression in primary tumors from 55 metastatic CRC patients, including 15 with mutant and 40 with wild‐type KRAS. Comparing these with normal colon tissue, we identified 49 miRNAs—including 19 novel miRNAs—significantly deregulated in tumor tissue. The presence of the KRAS mutation was associated with up‐regulation of miR‐127‐3p , miR‐92a , and miR‐486‐3p and down‐regulation of miR‐378 . Increased expression of miR‐127‐3p and miR‐92a in KRAS mutant tumors was significantly confirmed by quantitative reverse transcriptase polymerase chain reaction (qRT‐PCR) ( P < 0.05). We identified some predicted target genes of differentially expressed miRNAs between mutated and wild‐type KRAS , such as RSG3 and TOB1 , which are involved in apoptosis and proliferation. Target prediction and pathway analysis suggest a possible role for deregulated miRNAs in nicotinamide adenine dinucleotide phosphate (NADPH) regeneration and G protein‐coupled receptor signaling pathways. © 2011 Wiley Periodicals, Inc.