This patient, FR06, had received transarterial chemoembolization
(TACE) treatment, but as the other two TACE-treated patients did not present such Ixazomib molecular weight a profile we cannot make any conclusion on the effect of TACE on ABC expression. Second, we were able to demonstrate that in the 16 untreated patients the expression of 10 ABC transporters was significantly up-regulated in HCC compared with paired AHL samples. In untreated patients, only up-regulation of ABCC1 has been shown to be associated with a more aggressive HCC phenotype.10 To our knowledge this is the first publication reporting up-regulation of a broad range of ABC transporters in untreated HCC patients. This includes eight ABC genes: ABCA2, ABCB6, ABCC2, ABCC3, ABCC5, ABCC10, ABCC11, and ABCE1, whose association with HCC has not been reported
so far. Due to the size of some subpopulations, the described associations between ABC profile and clinical parameters will have to be confirmed on a larger patient population. Nevertheless, find more the results of the ABC profiling raise the question of the possible regulation pathways implicated in the phenomenon of ABC genes up-regulation. We chose to further investigate the possibility of miRNA-mediated ABC gene regulation in association with HCC. So far only miR-203 has been reported to specifically target ABCE127 but its implication in HCC still needs to be determined. Our miRNA screen in 10 HCC patients identified significant changes in expression of 90 miRNAs, including 11 up-regulated miRNAs and 79 down-regulated miRNAs, of which 25 had predicted ABC targets. Interestingly, 97% of the dysregulated miRNAs were highly conserved in mammals (up to the mouse), indicating their possible association with HCC, as has been shown for several diseases.31 Seventy-nine of 90 dysregulated miRNAs are down-regulated and this is in agreement with the evidence that miRNAs are generally down-regulated in cancer.32 Many miRNAs identified during the current screen confirmed findings obtained with larger
sample sets or sample sets coming from patients with a different medchemexpress cancer etiology. Similar to other publications, we observed down-regulation of miR-101,33 miR-122,34-37 miR-125a,37, 38 miR-130a,34, 39 miR-145,39-41 miR-199a,33, 36, 38, 39 miR-199b,38, 40 and up-regulation of miR-21.33-37, 40-42 Seventy-four percent of our patients had alcoholic cirrhosis, and ethanol-treatment has been linked in the literature to the miR-199 family.43 However, no correlation between the miRNA profiles and viral HCC etiology could be determined, probably due to the small patient size (14 alcohol, three HCV, one HBV, and one alcohol/HCV). Our screen also identified 12 miRNAs with predicted ABC targets that have not been previously associated with HCC. Down-regulated miRNAs were reported to be repressed by oncogenes: miR-145 by Ras,44 and miR-26a and miR-195 by Myc45 as well as let-7.