Involvement of miR-215 in colorectal cancer pathogenesis
| Název česky | Zapojení miR-215 do patogeneze kolorektálního karcinomu |
|---|---|
| Autoři | |
| Rok publikování | 2014 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Colorectal cancer (CRC) is one of the most common types of cancers worldwide and it is the third leading cause of cancer-related death in the western world. Therefore, several efforts have been made to find new biomarkers for early detection, accurate differentiation between clinical stages and better individualization of the therapy. MicroRNAs (miRNAs) are small, non-coding RNAs that post-transcriptionally regulate gene expression. They regulate many biological processes such as cell cycle, apoptosis, proliferation or invasivity and they can also affect anti-cancer therapy efficiency. They are differently expressed in normal and neoplastic colon tissues and can serve as a new prognostic and predictive biomarkers. However, only little is known about miRNAs target molecules and signaling pathways in which they are involved. We have analyzed expression profiles of 667 miRNAs in 8 patients diagnosed for CRC and 8 paired adjacent non-tumoral tissues using TaqMan Low Density miRNA arrays. We have found miR 215 to be one of the most deregulated miRNAs, therefore its expression was further validated on independent cohort of 250 paired samples and correlated with clinicopathological features of the patients. Afterwards, we investigated its involvement in CRC pathogenesis. We have overexpressed miR 215 in CRC cell lines and analyzed the effect on the viability, proliferation, cell cycle, apoptosis and migration of the cells. Subsequently, several targets of miR-215 have been identified and effects of this miRNA were analyzed also in vivo on mouse model. We have observed significantly decreased levels of miR-215 in primary CRC tissues and also in metastatic tissue. Moreover, we have found correlation between low expression of this miRNA and clinical stage and lymph node metastasis. In vitro analyses proved that higher levels of miR-215 lead to the arrest of cell cycle, increased apoptosis and reduced migration and proliferation of the cells. Using qRT-PCR we have identified several potential targets of miR-215 including XIAP, CD164 or HOXB9. The reduced expression of miR-215 has been observed in several tumor diseases, therefore we presume that this miRNA functions as an important tumor suppressor. The results of our study also indicated that miR-215 could serve as a new diagnostic biomarker and potential therapeutic target for treatment of CRC patients. |
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