HBXIP Regulates Mitochondrial Metabolism And Participates In Lung Cancer

Background:Lung cancer is the fastest growing type of cancer in terms of morbidity and mortality.Lung cancer,especialy NSCLC(Non-Small Cell Lung Cancer)places a huge burden on health care systems around the world.The exisiting treatments have different degrees of side-effects and the therapeutic effect is not satisfactory.The up-regulation of HBXIP(Hepatitis B X-interacting Protein)is observed in a variety of cancers,promoting the growth and metastasis of breast,cervical and liver cancers.Reasearch over the past decade has revealed a new link between metabolism and cancer progression,showed that metabolic structure will alter during tumorigenesis and metastasis.Recent advances in the field of cancer drug discovery have focused on the inhibitors of metabolic pathways.The study of metabolic reprogramming and its mechanism in the progression of lung cancer can provide the theoretical basis for the discovery of new drugs.Objective:To investigate the role of HBXIP in the development of NSCLC;To explore whether HBXIP plays an important regulatory role in the metastasis of lung cancer cells;To explore the molecular mechanism of HBXIP involved in the regulation of lung cancer cell metabolism.Methods:(1)The correlation between HBXIP and lung cancer was analyzed through TCGA database;(2)We used the constructed H1975 lung cancer cells with overexpression of HBXIP and the H1299 cells lung cancer cells with knockdown of HBXIP.The effect of HBXIP on the phenotype of lung cancer cells was detected by MTS,Transwell and Flow Cytometry.(3)We explored the regulation and mechanism of HBXIP on mitochondrial metabolism of lung cancer cells by Seahorse,Confocol,Western Blot,Co-IP.Results:Data analysis revealed that HBXIP was highly expressed in lung cancer and was associated with poor prognosis.We founded that up-regulation of HBXIP promoted the growth og lung cancer cells by MTS.Cell cycle and apoptosis detected by flow cytometry showed that HBXIP promoted the growth and inhibited apoptosis.Real-time PCR results showed that HBXIP facilitated the stemness of lung cancer cells.Teanswell assay was used to detect the migration ability of lung cancer cells,finding that HBXIP expression was proportional to the migration ability.H1975 overexpression of HBXIP caused significant decrease in epithelial markers and increase in mesenchymal markers.Detection of protein levels recealed that HBXIP could inhibit the activation of autophagy by the mTOR signaling pathway.HBXIP significantly inhibited the motichondrial function of lung cancer cells and promoted glycolysis,which may be realized through the interaction between HBXIP and NDUFV2.Significance:HBXIP plays an important role in promoting the development of lung cancer and can be used as a marker for the early diagnosis of lung cancer.This is the first time that we link HBXIP to mitochondria,and demonstrate that HBXIP inhibits mitochondrial function by acting with NDUFV2 to promote the progression of lung cancer.