H19 regulation of oestrogen induction of symmetric division is achieved by antagonizing Let-7c in breast cancer stem-like cells.

OBJECTIVES

Breast cancer stem-like cells (BrCSCs) are the major reason for tumour generation, resistance and recurrence. The turbulence of their self-renewal ability could help to constrain the stem cell expansion. The way BrCSCs divided was related to their self-renewal capacity, and the symmetric division contributed to a higher ability. Non-coding long RNA of H19 was involved in multiple malignant procedures; the role and mechanistic proof of non-coding long RNA of H19 in controlling the divisions of BrCSCs were barely known.

MATERIALS AND 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.