PDB is a tumor promotor and activator of protein kinase C. In human colonic T84 cells, pretreatment with PDB attenuated PGE1- stimulated Cl- secretion as measured by short circuit current (ΔISc, μA/cm2). MiRNAs are known to modulate a variety of proteins by degrading their mRNA or by inhibiting their translation. Since CFTR is the major Cl- channel in T84 cells, and CFTR-specific miRNAs have been identified, we examined if the PDB-attenuation of Cl- secretion involves miRNAs. Acute treatment with PDB significantly reduced 10μM PGE1-stimulated ISc (PGE1: 36.7±7.3; +200nM PDB, 20 min: 8.9±2.1; n蠅6). A 2 hour PDB exposure caused a similar reduction in PGE1-stimulated ISc (PGE1: 36.7±7.3; + 100nM PDB, 2h: 10 ±2.5; n=3). The 2hr treatment followed by an acute dose (100nM PDB 2h + 200nM PDB 20 min) still reduced the PGE1 prosecretory response (9± 4; n=3). This is possibly due to a reduction in the expression of CFTR since CFTR mRNA is also significantly reduced after 2h pretreatment with PDB (relative expression: Control: 3.56±0.7; PDB: 1.38±0.32; n>4). However this attenuation of CFTR function was lost with chronic treatment (100nM PDB, 24h: 18.7 ±8.4; 48h: 45.3 ±7.1; 72h: 32.7 ±13.8; n蠅3). Based on algorithm screening, we identified 6 miRNAs that may regulate CFTR: miR-145, -331, -384, -494, -1246 and -1290. Using a miRNA qRT-PCR Kit we compared the expression of these miRNAs in T84 cells treated with +100nM PDB for 2h. U6 snRNA was used as internal control. Although these miRNAs were expressed in T84 cells, PDB did not significantly alter their expression. Thus, it is unlikely that the common “CFTR-miRNAs” are involved in the PDB-induced attenuation of CFTR expression and function.