A novel AP-1/miR-101 regulatory feedback loop and its implication in the migration and invasion of hepatoma cells.
Bottom Line: Furthermore, reintroduction of miR-101 efficiently suppressed the AP-1 activity and pri-miR-101-2 transcription.These data thus suggest a novel AP-1/miR-101 regulatory circuitry, that is, AP-1 promotes the transcription of miR-101, whereas the expression of miR-101 reduces the level of ERK2 and c-Fos and thereby attenuates the AP-1 signaling.Further investigation disclosed that the AP-1 activator TPA-induced MMP9 activity and the TPA-promoted migration and invasion of hepatoma cells were significantly attenuated by miR-101 but were enhanced by miR-101 inhibitor.
Affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. China.Show MeSH
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Mentions: Consistently, overexpression of c-Jun andc-Fos enhanced the activity of p(−17.4/−16.4k) enhancer reporter, which was severely attenuated when the AP-1 binding sites were deleted (Figure 4A). Remarkably, miR-101 level was increased by ectopic expression of c-Fos and c-Jun, and was further enhanced by TPA treatment (Figure 4B and Supplementary Figure S5B). On the other hand, knockdown of c-Jun or/and c-Fos led to a dramatic decrease of the transcription activity of p(−17.4/−16.4k) (Figure 4C) and TPA-induced expression of miR-101 (Figure 4D), suggesting that the expression of miR-101 depends on the activity of AP-1.
Affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. China.