MicroRNA and MRNA profiling to identify metastatic biomarkers for colorectal cancers

Abstract

Most of cancer deaths are mainly due to the development of tumor metastasis rather than the primary lesion itself. MicroRNAs (miRNAs) play a diverse role in post transcriptional gene regulation of metastatic genes. The aim of this study was to identify differentially expressed miRNAs and mRNAs in primary colorectal cancer (CRC) with or without liver metastasis as compared to their neighboring non cancerous tissues. MiRNA profiling was performed on 24 samples using the LNA™ microRNA Array. Gene expression profiling was performed using the Affymetrix Human Gene 1.0 ST Array. The roles of several potential miRNA and mRNA candidates in tumour cell survival and metastasis cascade were further investigated by using miRNA inhibitors and mimics in CRC cell lines. To obtain high stringency results, five statistical test methods were used to analyze the microarray results. MAGIA2 integrated analysis was performed to determine miRNA-mRNA interactions. Thirteen significant differentially expressed miRNAs and 43 differentially expressed mRNAs were identified in CRC with or without metastasis compared with non-cancerous samples (p<0.05). MiR-182-5p was overexpressed in CRC and promoted cell migration and invasion through the ANLN and PDE4D pathways. MiR-203, miR-150-5p and miR-139-5p were downregulated in CRC and suppressed cell migration and invasion through the PDE4D, NEGR1 and ATP11A pathways respectively. Overexpressed miRNAs may function as oncogenes by downregulating tumor-suppressor genes that control cell differentiation or apoptosis, whereas the downregulated miRNAs act as tumor-suppressor by negatively regulating oncogenes that control cell differentiation or apoptosis. The discovery of these miRNAs and their targeted mRNAs in CRC metastasis to the liver has provided an insight into the novel mechanisms for regulating human gene expression that impacts diverse biological and pathological processes.