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Lentiviral delivery of a shRNA sequence analogous to miR‐4319/miR‐125‐5p induces apoptosis in NSCLC cells by arresting G2/M phase
Author(s) -
Xu Xuebo,
Lai Yueyang,
Zhou Wenzhao,
Hua Zichun
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28676
Subject(s) - small hairpin rna , a549 cell , apoptosis , rna interference , lentivirus , cell culture , cancer research , microrna , gene delivery , microbiology and biotechnology , cell , viral vector , gene knockdown , cell growth , biology , chemistry , transfection , virology , rna , gene , biochemistry , recombinant dna , virus , genetics , viral disease
In this study, we explored the therapeutic potential of microRNA (miR) analogs against non–small‐cell lung cancer (NSCLC) using lentiviral delivery of short hairpin RNA (shRNA). By using A549 as a model cell line, we used analogs and mimics of miR‐4319/miR‐125‐5p to target the tumorigenic RAF1 gene. Lentiviral vectors carrying shRNA of a highly efficient miRNA analog of miR‐4319/miR‐125‐5p, Analog2, were constructed to infect A549 cells. Our results showed that, compared with the noncancerous bronchial epithelial cell line 16HBE, lentivirus delivering Analog2 shRNA induced significant G2/M arrest and subsequent apoptosis in A549 cells, but not in 16HBE cells. Western blot analysis revealed that key factors regulating cell cycle were downregulated following RAF1 inhibition. In vivo xenograft experiments showed that lentivirus carrying Analog2 shRNA markedly decreased tumor size. Therefore, lentiviral delivery of Analog2 shRNA is a valid RNA interference‐based treatment against NSCLC with high potency and specificity.