--- - |2- 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. 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. - 'Journal of Cellular Physiology, Volume 234, Issue 2, Page 1904-1912, February 2019. '