The survival rates in colon cancer patients are inversely proportional to the number of lymph node metastases. The hypoxia-induced Epithelial to Mesenchymal Transition (EMT), driven by HIF1alpha, is known to be involved in cancer progression and metastasis. Recently, we have reported that miR-675-5p promotes glioma growth by stabilizing HIF1alpha; here, by use of the syngeneic cell lines we investigated the role of the miR-675-5p in colon cancer metastasis.Our results show that miR-675-5p, over expressed in metastatic colon cancer cells, participates to tumour progression by regulating HIF1alpha induced EMT. MiR-675-5p increases Snail transcription by a dual strategy: i) stabilizing the activity of the transcription factor HIF1alpha and ii) and inhibiting Snail's repressor DDB2 (Damage specific DNA Binding protein 2).Moreover, transcriptional analyses on specimens from colon cancer patients confirmed, in vivo, the correlation between miR-675-5p over-expression and metastasis, thus identifying miR-675-5p as a new marker for colon cancer progression and therefore a putative target for therapeutic strategies.
MiR-675-5p supports hypoxia induced epithelial to mesenchymal transition in colon cancer cells.
Alessandro Riccardo;
2017
Abstract
The survival rates in colon cancer patients are inversely proportional to the number of lymph node metastases. The hypoxia-induced Epithelial to Mesenchymal Transition (EMT), driven by HIF1alpha, is known to be involved in cancer progression and metastasis. Recently, we have reported that miR-675-5p promotes glioma growth by stabilizing HIF1alpha; here, by use of the syngeneic cell lines we investigated the role of the miR-675-5p in colon cancer metastasis.Our results show that miR-675-5p, over expressed in metastatic colon cancer cells, participates to tumour progression by regulating HIF1alpha induced EMT. MiR-675-5p increases Snail transcription by a dual strategy: i) stabilizing the activity of the transcription factor HIF1alpha and ii) and inhibiting Snail's repressor DDB2 (Damage specific DNA Binding protein 2).Moreover, transcriptional analyses on specimens from colon cancer patients confirmed, in vivo, the correlation between miR-675-5p over-expression and metastasis, thus identifying miR-675-5p as a new marker for colon cancer progression and therefore a putative target for therapeutic strategies.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.