Conclusions
Our results revealed a previously undescribed double negative feedback loop between sponge H19 and targeted Let-7c through oestrogen activated Wnt signalling that dominated in stem cells' division.
Methods
Indicative functions of H19 in preclinical study were analysed by using the TCGA data base. Division manners were defined by using fluorescence staining.
Results
We identified the stimulation of H19 on symmetric division of BrCSCs, which subsequently resulted in self-renewing increasing. H19 inhibited the Let-7c availability by acting as its specific molecular sponge, and with Let-7c inhibition, oestrogen receptor activated Wnt signalling was unconstrained. Similarly, restoring Let-7c constrained oestrogen receptor activated Wnt factors, which sequentially inhibited the H19 decreasing of Let-7 bioavailability. Let-7c is reactivated in vitro where H19 was knockdown, and later inhibited the symmetric division of BrCSCs. Reciprocally, Wnt pathway activation leads to H19 increasing, which in turn decreased Let-7c bioavailability. Conclusions: Our results revealed a previously undescribed double negative feedback loop between sponge H19 and targeted Let-7c through oestrogen activated Wnt signalling that dominated in stem cells' division.