In this study, we modify the SWCNT with PEG-2000 and conjugate an anti-MALAT1 oligo to it, test the delivery of this compound in vitro, inject it intravenously into a disseminated MM mouse model, and observe a significant inhibition of MM progression, which indicates that SWCNT is an ideal delivery shuttle for anti-MALAT1 gapmer DNA.
LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well known protooncogene, has be shown to be upregulated in various tumor types, including multiple myeloma.
Furthermore, using novel single-wall carbon nanotube (SWCNT) conjugated with anti-MALAT1 oligos, we successfully knocked-down MALAT1 RNA in cultured MM cell lines and xenograft murine models.
Our findings demonstrate a crucial role of MALAT1 in the regulation of the proteasome machinery, and provide proof-of-concept that its targeting is a novel powerful option for the treatment of MM.
In addition, silencing of MALAT1 by intratumoral injection of MALAT1 shRNA attenuated the tumour growth in mice bearing myeloma xenograft and led to massive apoptosis in the xenograft tumour.
Our study identified 31 lncRNAs deregulated in tumor samples compared to normal controls; among these, the upregulation of MALAT1 appeared associated in MM patients with molecular pathways involving cell cycle regulation, p53-mediated DNA damage response, and mRNA maturation processes.
Our knowledge of the role of MALAT1 in cellular transformation is pointing toward its potential use as a biomarker and a target for novel therapeutic approaches in multiple myeloma.
This study aimed to investigate the role and clinical relevance of the long non-coding RNA (lncRNA), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in multiple myeloma.