E2F3 and colorectal carcinoma: Mir-497, miR-139-5p, and mir-23a sensitize CRC cells to 5-FU by serving as tumor suppressors.84,85 The suppression of mir-31 declines the resistance to 5-FU in HCT116 cells.10 Mir-129 leads CRC cells to be sensitized to 5-FU in vitro and in vivo in two ways; either by (i) downregulating Bcl-2 expression, which leads to high apoptosis rate; or by (ii) suppressing the E2F3 protein.63 Mir-139-5p sensitizes CRC cells to 5-FU through inducing apoptosis and inhibiting the expression of miR-139-5p targets NOTCH-1 gene and its downstream MDR-associated genes, MRP-1, and Bcl-2 .85