Abstract
MicroRNA (miR)-1246 is abnormally expressed and has pro-oncogenic functions in multiple types of cancer. In the present study, its functions in breast cancer and the underlying mechanisms were further elucidated. The clinical relevance of miR-1246 was analyzed and its expression in clinical specimens and cell lines was examined by reverse transcription-quantitat000000ive PCR analysis. FACS was used to detect cell apoptosis and mitochondrial transmembrane potential. A Transwell system was used to detect cell migration and invasion. Luciferase assay was used to confirm the target gene of miR-1246. Xenograft and metastasis mouse models were constructed to determine the function of miR-1246 in vivo. miR-1246 was found to be negatively associated with overall survival in breast cancer. miR-1246 inhibitor could effectively increase the cytotoxicity of docetaxel (Doc) by inducing apoptosis, and impair cell migration and invasion by suppressing epithelial-to-mesenchymal transition. Nuclear factor (erythroid 2)-like factor 3 (NFE2L3) was confirmed as a new target gene of miR-1246, and its overexpression was shown to reduce drug resistance and migration of MDA-MB-231 cells. More importantly, NFE2L3-silencing attenuated the effect of miR-1246 inhibitor. Finally, the inhibition of miR-1246 effectively enhanced the cytotoxicity of Doc in xenografts and impaired breast cancer metastasis. Therefore, miR-1246 may promote drug resistance and metastasis in breast cancer by targeting NFE2L3.
Highlights
Breast cancer is the second most common cause of cancer mortality among women [1]
Our previous study revealed that serum miR-1246 levels in patients with breast cancer were elevated, as compared with those in healthy controls [11]
Bott et al analyzed the data from a METABRIC miRNA-expression dataset [19] to screen the miRNAs those were significantly correlated with the overall survival of patients with breast cancer [18]
Summary
Breast cancer is the second most common cause of cancer mortality among women [1]. Chemotherapy is a critical therapeutic approach for breast cancer, and various chemotherapeutic agents are used for this purpose. Almost all patients with breast cancer can develop drug resistance, which comprises one of the most serious challenges in cancer treatment [2]. It is believed that the overall survival of cancer patients could be effectively improved if drug resistance could be overcome [3]. Metastasis, another unique characteristic of cancer progression, is the primary cause of breast cancer morbidity and mortality [4].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
