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KMID : 0578320160390040299
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Molecules and Cells
2016 Volume.39 No. 4 p.299 ~ p.309
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miR-30a Regulates the Expression of CAGE and p53 and Regulates the Response to Anti-Cancer Drugs
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Park Deok-Bum
Kim Hyun-A
Kim Young-Mi
Jeoung Doo-Il
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Abstract
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We have previously reported the role of miR-217 in anti-cancer drug-resistance. miRNA array and miRNA hybridization analysis predicted miR-30a-3p as a target of miR-217. miR-30a-3p and miR-217 formed a negative feedback loop and regulated the expression of each other. Ago1 immunoprecipitation and co-localization analysis revealed a possible interaction between miR-30a-3p and miR-217. miR-30a-3p conferred resistance to anti-cancer drugs and enhanced the invasion, migration, angiogenic, tumorigenic, and metastatic potential of cancer cells in CAGE-dependent manner. CAGE increased the expression of miR-30a-3p by binding to the promoter sequences of miR-30a-3p, suggesting a positive feedback loop between CAGE and miR-30a-3p. miR-30a-3p decreased the expression of p53, which showed the binding to the promoter sequences of miR-30a-3p and CAGE in anti-cancer drug-sensitive cancer cells. Luciferase activity assays showed that p53 serves as a target of miR-30a. Thus, the miR-30a-3p-CAGE-p53 feedback loop serves as a target for overcoming resistance to anti-cancer drugs.
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KEYWORD
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anti-cancer drug-resistance, CAGE, feedback loop, miR-30a, p53
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