Structure of LINC00511-siRNA-conjugated nanobubbles and improvement of cisplatin sensitivity on triple negative breast cancer

FASEB J. 2020 Jul;34(7):9713-9726. doi: 10.1096/fj.202000481R. Epub 2020 Jun 4.

Abstract

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.

Keywords: RNA-Seq; drug resistance; gene transfection; nanobubbles; triple negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Cell Proliferation
  • Cisplatin / chemistry
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm*
  • Humans
  • Nanostructures / administration & dosage*
  • Nanostructures / chemistry*
  • RNA, Long Noncoding / chemistry
  • RNA, Long Noncoding / genetics*
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / genetics*
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / pathology
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Cisplatin