Targeting DNAJC19 overcomes tumor growth and metastasis in NSCLC by regulating AKT1 signaling.

Abstract

e15024 Background: Some driver oncogenes are still unknown in non-small cell lung cancer (NSCLC). DNAJC19, known as a major component of the translocation machinery of mitochondrial membranes, is a disease-associated protein. Herein, we reported the role of DNAJC19 in NSCLC cell growth and metastasis. Methods: Immunohistochemistry (IHC) was performed to investigate DNAJC19 expression in NSCLC clinical samples. For knockdown or overexpression assays in A549 or NCI-H1299 lung cancer cells, lentiviral vectors were used. After assessment of cell functions, DNAJC19-knockdown A549 cells were further applied to establish mice xenograft and metastasis tumor models. STRING database, western, PCR, immunoprecipitation and IHC were performed for the mechanistic study. Results: Expression of DNAJC19 was higher in tumors than non-cancerous adjacent tissues. Survival analysis found that low DNAJC19 levels were correlated with increased progression-free survival rate. ShRNA-mediated knockdown of DNAJC19 markedly inhibited cell growth, viability, migration and invasion. Moreover, RNA-seq analysis explored that PI3K/AKT signaling pathway was involved in molecular events when A549 cells treated with shDNAJC19. And then DNAJC19 knockdown also decreased AKT1 expression in A549 cells. In addition, cellular functions were greatly rescued in DNAJC19-knockdown A549 cells by exotic overexpression of AKT1. Furthermore, tumor xenograft growth and metastasis were markedly repressed in the shDNAJC19 group than control group. As expected, DNAJC19 and AKT1 expression levels in xenograft mice samples were also lower in the shDNAJC19 group than in the shCtrl group. Conclusions: DNAJC19 greatly promotes NSCLC cell growth and metastasis via regulating AKT1 signaling, providing a novel therapeutic target for NSCLC patients.