OXCT1 Promotes Proliferation And Migration Of Non-small Lung Cancer Cell Migration Via Activating NF-κB Pathway

Lung cancer is one of the most common malignant tumors and poses a great threat to human health.Lung cancer could be divided into small cell lung cancer(NSCLC)and non-small cell lung cancer(NSCLC),and non-small cell lung cancer accounts for about 80%-85% of lung cancer.Therefore,it is urgent to find new target of non-small cell lung cancer.The ketone body,produced by the liver,is transported through the blood to other organs and tissues,as the fuel of the cell during starvation.OXCT1(3-oxoacid CoA-transferase 1),which is located in the mitochondria of the extrahepatic tissue,is the rate-limiting enzyme of ketolysis.According to report,in the liver cancer cells,OXCT1 could be reactivated by the mTORC2-AKT-SP1 pathway to maintain the growth of liver cancer cells under the condition of serum starvation.Moreover,there have been many reports that OXCT1 is up-regulated in kinds of tumors.We found that the protein level of OXCT1 was highly expressed in the cell lines and tissues of NSCLC.Knocking down could inhibit the growth and migration of non-small cell lung cancer cells and induce cell apoptosis.Meanwhile,we found that the knockdown of OXCT1 decreased the cellular ATP production,and the number of mitochondria was reduced.Furthermore,we found that silencing OXCT1 decreased protein levels of phosphorylated IKKα/β and IκBα,increased expression of IκBα,and protein level of phosphorylated-p65 was decreased,then the expression level of MMP2 and MMP9,migration-related genes,which are p65 transcribed,were also decreased.And it could indicate that OXCT1 affected the growth and migration of NSCLC via the classical pathway of NF-κB.In conclusion,our research has demonstrated the indispensable role of OXCT1 for the development in NSCLC.It provides adequate theoretical basis for the treatment of non-small cell lung cancer with OXCT1 as a target.