Open AccessIdentification and functional screening of micro RNA s highly deregulated in colorectal cancer
Author(s) -
Faltejskova Petra,
Svoboda Marek,
Srutova Klara,
Mlcochova Jitka,
Besse Andrej,
Nekvindova Jana,
Radova Lenka,
Fabian Pavel,
Slaba Katerina,
Kiss Igor,
Vyzula Rostislav,
Slaby Ondrej
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2012.01579.x
Subject(s) - microrna , oncogene , colorectal cancer , cancer research , ectopic expression , pathogenesis , biology , cancer , cell cycle , apoptosis , medicine , cell culture , immunology , gene , genetics
Micro RNA s (mi RNA s) constitute a robust regulatory network with post‐transcriptional regulatory efficiency for almost one half of human coding genes, including oncogenes and tumour suppressors. We determined the expression profile of 667 mi RNA s in colorectal cancer ( CRC ) tissues and paired non‐tumoural tissues and identified 42 differentially expressed mi RNA s. We chose miR‐215, miR‐375, miR‐378, miR‐422a and miR‐135b for further validation on an independent cohort of 125 clinically characterized CRC patients and for in vitro analyses. MiR‐215, miR‐375, miR‐378 and miR‐422a were significantly decreased, whereas miR‐135b was increased in CRC tumour tissues. Levels of miR‐215 and miR‐422a correlated with clinical stage. MiR‐135b was associated with higher pre‐operative serum levels of CEA and CA 19‐9. In vitro analyses showed that ectopic expression of miR‐215 decreases viability and migration, increases apoptosis and promotes cell cycle arrest in DLD ‐1 and HCT ‐116 colon cancer cell lines. Similarly, overexpression of miR‐375 and inhibition of miR‐135b led to decreased viability. Finally, restoration of miR‐378, miR‐422a and miR‐375 inhibited G1/S transition. These findings indicate that miR‐378, miR‐375, miR‐422a and miR‐215 play an important role in CRC as tumour suppressors, whereas miR‐135b functions as an oncogene; both groups of mi RNA contribute to CRC pathogenesis.