LncRNA TTN-AS1 confers tamoxifen resistance in breast cancer via sponging miR-107 to modulate PI3K/AKT signaling pathway.

Objective: Tamoxifen resistance of breast cancer (BC) is a significant hindrance in clinical therapy. The long-noncoding RNA (lncRNA) TTN-AS1 has been reported as a crucial tumor promoting factor in various cancers. In this study, we set out to discover the specific pathologic regulatory mechanisms of tamoxifen-resistance in breast cancer.

Methods: MTT assay was conducted to evaluate the cell viability of the breast cancer cell lines MCF-7 and MCF-7/TAM. QRT-PCR and western blot assay were performed to estimate the expression of TTN-AS1, miR-107 and related proteins. Flow cytometry was conducted to identify degree of apoptosis and cell cycle. The invasive ability was estimated by transwell chamber assay.

Results: Our findings revealed that TTN-AS1 can enhance tamoxifen-resistance in BC cells and augment the invasive ability of tamoxifen-resistant breast cancer cells by down-regulating miR-107, and thereby encourage the development of drug-resistant BC. Further investigation indicates that lncRNA TTN-AS1 worsens the course of tamoxifen-resistant BC by regulating zinc and ring finger 2 (ZNRF2) via miR-107 and activating the PI3K/AKT pathway.

Conclusion: Our findings suggest that the lncRNA TTN-AS1 can encourage tamoxifen-resistance in BC by modulating the miR-107/ZNRF2 axis and stimulating the PI3K/AKT pathway.