Inhibitory role of large intergenic noncoding RNA-ROR on tamoxifen resistance in the endocrine therapy of breast cancer by regulating the PI3K/Akt/mTOR signaling pathway.

Breast cancer (BC) is the second-leading cause of central nervous system metastases among severe malignancies. This study aimed at investigating the underlying mechanism by which large intergenic noncoding RNA-regulator of reprogramming (lincRNA-ROR) affects the tamoxifen (TAM) resistance of BC cells by regulating the PI3K/Akt/mTOR signaling pathway. Immortalized human mammary epithelial cell line (MCF10A) and BC cell lines (MCF-7, MDA-MB-231, T47D, BCAP-37, and ZK-75-1) were cultured, and BC tissues and adjacent normal breast tissues were collected from 152 BC patients. LincRNA-ROR expression in tissues and cells were detected using reverse transcription quantitative polymerase chain reaction. RNA interference was used to silence lincRNA-ROR in MDA-MB-231 cells, and then the cell proliferation and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and annexin-V and propidium iodide (PI) double staining respectively. The expression of apoptosis-related proteins and PI3K/Akt/mTOR signaling pathway-related proteins was measured by performing western blot assay. The BC tissues and cells presented a higher expression of lincRNA-ROR. MAD-MB-231 cells exhibited the highest lincRNA-ROR expression. After lincRNA-ROR silencing, MAD-MB-231 cells showed decreased proliferation, and increased sensitivity to TAM. Besides, the apoptosis-promoting effect of TAM on MAN-MB-231 cells significantly increased. The expression of PI3K/Akt/mTOR signaling pathway-related proteins and the PI3K/Akt/mTOR signaling pathway were repressed by TAM after silencing lincRNA-ROR. Our study demonstrated that silencing lincRNA-ROR could increase the sensitivity of BC MAD-MB-231 cells to TAM by suppressing the activation of P13K/Akt/mTOR signaling pathway.