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WOS: 000485707300011, BACKGROUND/AIMS Breast cancer is the most common type of cancer in women and is among the leading causes of cancer-related deaths. Long non-coding RNAs (lncRNAs) play significant roles in cell proliferation, transcriptional regulation, cell cycle progression, apoptosis, carcinogenesis, and metastasis. Studies have shown that ponatinib has an antiproliferative effect in some types of cancer. The aim of the present study was to evaluate the effect of ponatinib on cytotoxicity and to determine changes in lncRNA expression levels with the use of ponatinib treatment in estrogen receptor (ER)-independent MDA-MB-231 and ER-dependent MCF-7 breast cancer cells. MATERIAL and METHODS The cytotoxic effects of ponatinib were determined by using the xCELLigence system. Changes in lncRNA expression profiles were determined using quantitative reverse transcription polymerase chain reaction to investigate the antiproliferative roles of ponatinib in breast cancer. RESULTS In human breast adenocarcinoma cell lines (MCF-7 and MDA-MB-231), the IC50 doses of ponatinib were determined to be 4.59 mu M (72 h) and 1.41 mu M (48 h), respectively. After ponatinib treatment, we observed changes in lncRNA expression profiles in ER-independent MDA-MB- 231 and ER-dependent MCF-7 breast cancer cells compared with the control group. CONCLUSION The changes in the lncRNA expression profiles and the anti-cancer agent of ponatinib play roles in the definition of therapeutic target for new approach in breast cancer.