| Autor: |
Zhang, Yizhou, Takahashi, Shoichi, Tasaka, Akiko, Yoshima, Tadahiko, Ochi, Hidenori, Chayama, Kazuaki |
| Předmět: |
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| Zdroj: |
Journal of Gastroenterology & Hepatology; Mar2013, Vol. 28 Issue 3, p565-575, 11p, 1 Diagram, 1 Chart, 5 Graphs |
| Abstrakt: |
Background and Aim Changes in micro RNA (mi RNA) expression have been detected in a broad range of biological processes including cancer. Here we determined the role of mi RNA dysregulation in hepatocellular carcinoma ( HCC). Methods We investigated the expression of nine cancer-related mi RNAs in HCC. Among these, mi R-224 was the most significantly uprgulated in HCC tissues ( n = 18), compared with normal ( n = 9) and HCC adjacent non-tumorous liver tissues ( n = 18). After leading-in currently reported gene targets from Sanger mi RBase, we characterized the expression profiles of target genes of mi R-224 using c DNA microarray. The altered expression was subsequently validated by real-time polymerase chain reaction and Western blot. The phenotypic changes by mi R-224 expression were identified by cell viability, apoptosis, and in vitro scratch assays. Results The microarray analysis and mi RNA target prediction analysis allowed the identification of significant changes in 68 putative gene targets after overexpression of mi R-224. The high-ranking genes CDC42, CDH1, PAK2, BCL-2, and MAPK1 were confirmed as important targets of mi R-224 and involvement in hepatocarcinogenesis. Overexpression of mi R-224 significantly in Hek293 and Huh7 cells altered the expression levels of CDC42, CDH1, PAK2, and BCL-2 at both m RNA and protein levels. Similar changes in the expression of the same genes were also observed in HCC tissues. Via functional analyses, cell proliferation, migration and anti-apoptosis were proved to be affected by mi R-224 expression. Conclusion The results suggest that mi R-224 plays a role in cell proliferation, migration, invasion, and anti-apoptosis in HCC by directly binding to its gene targets, implicating this RNA in HCC development and progression. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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