Background

MicroRNAs (miRNAs) are 19-25 nucleotides non-coding RNA molecules, which act by silencing the expression of their target genes. These non-coding RNAs regulate central mechanisms of tumorigenesis such as apoptosis, stress responses, proliferation and differentiation processes. Functional studies have shown that miRNAs contribute to tumour development by gain or loss of their function due to mutations or altered expression. In CRC, several studies have listed differentially expressed miRNAs. However, the leading cause of miRNAs aberrant expression and their contribution in CRC progression have not been elucidated, as no studies have described the underlying biology of the progression of this disease.

Aim

The aim of our study is to identify and characterize miRNAs involved in colorectal progression, and determine through which mechanisms they contribute to its progression.

Plan of work

1. Identification of  miRNAs involved in CRC progression by miRNAs expression studies
2. Characterization of the (epi)genetic changes that lead to altered expression of the miRNAs (methylation specific PCR (MSP), multiplex ligation-depended probe amplification (MLPA),quantitative RT-PCR, mutation analysis and in silico transcription factors binding sites)
3. Identification of the miRNAs target genes in silico (integration of miRNA and mRNA expression studies and specific target prediction software (TargetScan)) and experimentally (cell transductions, inmmunoblot analysis, quantitative RT-PCR)

Duration

Minimum 6 months

Contact

For more information please contact dr. R.J.A. Fijneman