Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5505868 | Biochemical and Biophysical Research Communications | 2017 | 7 Pages |
Abstract
CD44 and miR-221 are upregulated in hepatocellular carcinoma (HCC) cell lines and tumors, however a connection between the two has not been identified. As the expression of miR-221 directly correlated with CD44 in HCC cells, we hypothesized that miR-221 may directly or indirectly regulate CD44 expression. Inhibition of miR-221 with antisense in Sk-Hep-1 or SNU-449Â cell lines reduced CD44 protein expression while miR-221 mimic increased CD44 protein levels. miR-221 antisense did not alter the CD44 mRNA levels in Sk-Hep-1 or SNU-449Â cells suggesting that regulation of CD44 protein occurs post transcriptionally. To discover miRNAs that may be involved in the miR-221 regulation of CD44, we performed miRNA profiling in SNU-449Â cells treated with anti-miR-221. Several miRNAs were increased with miR-221 inhibition including miR-708-5p, a miRNA that targets CD44. As miR-221 targets several regulators of the PI3K-AKT-mTOR pathway and a link between this pathway and CD44 has been previously shown in prostate cancer, we considered miR-221 regulation of CD44 may be through this pathway. Inhibition of miR-221 reduced p-4EBP1, a downstream effector of the PI3K-AKT-mTOR pathway. Likewise, inhibiting the PI3K-AKT-mTOR pathway with the ATP-competitive mTOR inhibitor PP242 reduced CD44 protein in SNU-423 and SNU-449Â cells without altering CD44 mRNA levels.
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Authors
Jihye Kim, Jinmai Jiang, Mohamed Badawi, Thomas D. Schmittgen,