An Antisense Oligonucleotide Drug Targeting miR-21 Induces H1650 Apoptosis and Caspase Activation.
Technol Cancer Res Treat
; 18: 1533033819892263, 2019.
Article
em En
| MEDLINE
| ID: mdl-31818225
ABSTRACT
Non-small cell lung cancer is the most common malignant tumor in the world. Currently, chemotherapy is still the major method for non-small cell lung cancer treatment, but the problem of cancer drug resistance still exists, so we designed 5 different phosphorothioate oligonucleotides to silence key genes in tumor cell development, which could help avoid inducing cancer cell drug resistance. MicroRNAs have been shown to play a crucial role in the pathogenesis and progression of many malignancies, such as breast, colon, lung, and pancreatic cancer. According to the data from the Gene Expression Omnibus database, miR-21 has been reported to be one of the top 20 differentially expressed microRNAs screened using the Morpheus online tool, and miR-21 has been revealed to regulate a series of biological behaviors in cancer cells, including cell proliferation, migration, invasion, metastasis, and apoptosis. In recent years, gene therapy has emerged as a new therapeutic strategy for cancer treatment. Antisense oligonucleotides have recently been suggested as a novel approach for targeting microRNAs by antisense-based gene silencing. Five phosphorothioate oligonucleotides were designed, synthesized, and screened for anticancer activity. Reverse transcription-polymerase chain reaction was used to detect the relative expression of miR21. Among these 5 sequences, only phosphorothioate oligonucleotide 4 inhibited the proliferation of H1650 cells, and this effect was due to the induction of cancer cell apoptosis by activating the caspase-8 apoptotic pathway. In conclusion, this research confirmed the anticancer activity of phosphorothioate oligonucleotide 4 and revealed the underlying mechanism, which has the potential to be a novel anticancer strategy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligonucleotídeos Antissenso
/
Apoptose
/
Caspases
/
MicroRNAs
/
Interferência de RNA
Limite:
Humans
Idioma:
En
Revista:
Technol Cancer Res Treat
Ano de publicação:
2019
Tipo de documento:
Article