Nanoparticles (NPs)-mediated lncBCMA silencing to promote eEF1A1 ubiquitination and suppress breast cancer growth and metastasis.

Autor:	Yang K; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.; Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-sen Memorial Hospital, Foshan 528200, China., Xu L; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.; Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-sen Memorial Hospital, Foshan 528200, China., Xu Y; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.; Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China., Shen Q; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.; Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-sen Memorial Hospital, Foshan 528200, China.; Department of Clinical Pharmacology, the Second Affiliated Hospital, University of South China, Hengyang 421001, China., Qin T; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.; Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.; Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China., Yu Y; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.; Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.; Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China., Nie Y; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.; Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China., Yao H; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.; Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.; Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China., Xu X; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.; Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-sen Memorial Hospital, Foshan 528200, China.
Jazyk:	angličtina
Zdroj:	Acta pharmaceutica Sinica. B [Acta Pharm Sin B] 2023 Aug; Vol. 13 (8), pp. 3489-3502. Date of Electronic Publication: 2022 Dec 10.
DOI:	10.1016/j.apsb.2022.12.004
Abstrakt:	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. (© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu