Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China.
Department of Interventional Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China.
FASEB J. 2020 Jul;34(7):9713-9726. doi: 10.1096/fj.202000481R. Epub 2020 Jun 4.
The drug resistance of triple negative breast cancer (TNBC) is considered as a major obstacle for the curative effect of chemotherapy. Long intergenic noncoding RNA 00511 (LINC00511) has been considered as a target gene of drug resistance. A novel theranostic agent loaded with LINC00511-siRNA to deliver siRNA was structured, and the responses of drug sensitivity in TNBC were detected. Next-generation high-throughput RNA sequencing (RNA-Seq) was performed to accurately analyze the differential expression of mRNAs and lncRNA targets after LINC00511-siRNA transfection with low-frequency ultrasound (LFUS). The LINC00511-siRNA conjugated nanobubble complexes showed appropriate characterization, with a mean diameter of 516.1 ± 24.7 nm and a zeta potential of -38.05 ± 0.24 mV. The transfection efficiency of nanobubble complexes was approximately 50% with LFUS. By RNA-Seq, the differential expressions of lncRNA transcripts and mRNA transcripts were identified, and then analyzed. The GO and KEGG enrichment analyses revealed the TNBC drug resistance related target genes and pathways. The combination of LFUS irradiation and nanobubble complexes is regarded as an efficient and safe method for siRNA transfection. The TNBC drug resistance occurs as a result of synergistic reactions between a variety of genes and a variety of pathways.
三阴性乳腺癌(TNBC)的耐药性被认为是化疗疗效的主要障碍。长链非编码 RNA 00511(LINC00511)已被认为是耐药性的靶基因。构建了一种新型载有 LINC00511-siRNA 的治疗药物递送系统,并检测了 TNBC 对药物敏感性的反应。采用低频超声(LFUS)对 LINC00511-siRNA 转染后差异表达的 mRNAs 和 lncRNA 靶标进行了高通量 RNA 测序(RNA-Seq)分析。LINC00511-siRNA 偶联纳米泡复合物具有适当的特性,平均直径为 516.1±24.7nm,zeta 电位为-38.05±0.24mV。LFUS 可使纳米泡复合物的转染效率达到约 50%。通过 RNA-Seq 鉴定并分析了 lncRNA 转录本和 mRNA 转录本的差异表达。GO 和 KEGG 富集分析揭示了与 TNBC 耐药相关的靶基因和通路。LFUS 照射和纳米泡复合物的联合被认为是一种有效的、安全的 siRNA 转染方法。TNBC 耐药性的发生是多种基因和多种途径协同作用的结果。