RESUMO
Long non-coding RNAs (lncRNAs) play an important role in cancer metastasis. Exploring metastasis-associated lncRNAs and developing effective strategy for targeted regulation of lncRNA function in vivo are of utmost importance for the treatment of metastatic cancer, which however remains a big challenge. Herein, we identified a new functional lncRNA (denoted lncBCMA), which could stabilize the expression of eukaryotic translation elongation factor 1A1 (eEF1A1) via antagonizing its ubiquitination to promote triple-negative breast cancer (TNBC) growth and metastasis. Based on this regulatory mechanism, an endosomal pH-responsive nanoparticle (NP) platform was engineered for systemic lncBCMA siRNA (siBCMA) delivery. This NPs-mediated siBCMA delivery could effectively silence lncBCMA expression and promote eEF1A1 ubiquitination, thereby leading to a significant inhibition of TNBC tumor growth and metastasis. These findings show that lncBCMA could be used as a potential biomarker to predict the prognosis of TNBC patients and NPs-mediated lncBCMA silencing could be an effective strategy for metastatic TNBC treatment.
RESUMO
Thyroid carcinomas are the most common endocrine malignancies,and the overwhelming majority of them is differentiated thyroid carcinoma (DTC).The major therapies of DTCs are surgical resection,thyroid stimulating hormone (TSH) inhibitory treatment and iodine radioisotope (131I) treatment.131I has been widely applied for the diagnosis and treatment of DTC,however,part of these patients may reduce or loss the uptake capacity of 131I owing to the alteration of sodium-iodide symporter gene,BRAF,paired box 8,microRNA and cytokeratin 19.These genes are particularly important in the treatment of DTC,which can be used as biomarkers in the treatment efficacy evaluation.