Runt-related transcription factor 1 contributes to lung cancer development by binding to tartrate-resistant acid phosphatase 5. Issue 23 (2nd December 2019) - He, Changjun
ABSTRACT: Lung cancer (LC) is one of the malignant tumors with growing morbidity and mortality. The involvement of runt-related transcription factor 1 (RUNX1) in LC patients has been elucidated. We intended to research mechanisms of RUNX1 and tartrate-resistant acid phosphatase 5 (ACP5) in LC. Firstly, ACP5 levels in LC tissues, paracancerous tissues, LC cells and tracheal epithelial cells were detected. RUNX1 overexpression plasmid and interference plasmid were constructed and transfected into 95C cells and A549 cells, respectively. The binding of RUNX1 to ACP5 promoter was tested. Additionally, the gain- and loss-of-function were performed to explore the effects of ACP5 and RUNX1 on LC biological process. The xenograft tumor in nude mice was constructed in vivo to verify in vitro results. Functional rescue experiment was performed by adding MAPK-specific activator P79350 to A549 cells with si-ACP5 to measure the effects of ERK/MAPK axis on LC progression. Consequently, we found ACP5 expression was higher in LC tissues and cells, and ACP5 silencing suppressed LC cell growth. Overexpression of ACP5 promoted malignant biological behavior of LC cells. RUNX1 could bind to ACP5 promoter, and overexpressed RUNX1 promoted ACP5 expression and LC cell growth. Moreover, ACP5 upregulated the ERK/MAPK axis and thus promoted LC progression. The results of xenograft tumor in nude mice showed that silencing ACP5 could inhibit the growth of LC cells in vivo . To conclude, silenced RUNX1 inhibits LC progression through the ERK/MAPK axis by binding to ACP5. This study may provide new approaches for LC treatment.