Proposed model of how the inflammation pathway can promote colorectal cancer progression by linking inflammation to downregulation of PDCD4 via miR-21 induction mediated by COX-2 driven accumulation of PGE₂.

<p>Persistent inflammation at the tumour site drives increase in COX-2 expression leading to accumulation of PGE₂. This in turn leads to the increase in expression of miR-21 and subsequent downregulation of PDCD4 protein levels facilitating progressive increase to more invasive and metastatic forms of colorectal cancer (from Dukes' A to B, C and D). Our experiments indicate that this pathway can be blocked by COX-2 inhibitors (NS398 and Aspirin) by preventing accumulation of PGE₂ as well as by miR-21 inhibitors. ↑ Activation, Inhibition. See text for further details.