LAPTM4B Promotes Autophagy Through Regulation Of ATG3 In Hepatocellular Carcinoma

BackgroundHepatocellular carcinoma(HCC)is one of the most common malignances with high morbidity and mortality worldwide.There are not obvious symptoms in the early stage of HCC.Although advancement of the diagnosis and treatment of HCC have been made,the overall survival rate of patients with HCC remains poor.Therefore,it is urgently needed to identify novel therapeutic targets.Autophagy play crucial role in the turmorgenesis and development of cancers.It has been reported that autophagy can regulate the growth,metastasis and energy metabolism of HCC.LAPTM4B(Lysosomal Transmembrane Protein 4 beta)exerts oncogenic activity in tumors,such as promoting cell proliferation,migration,invasion and inhibition of cell apoptosis.LAPTM4B also induce anthracycline intracellular retention,reduce injury drugs on DNA,and affect the stability of the lysosomal membrane.Recent studies demonstrated that LAPTM4B is involved in cell autophagy.However,the underlying molecular mechanisms by which LAPTM4B regulates autophagy remain elucidated.Methods and results1.We performed qPCR to detect the expression of LAPTM4B in 60 pairs of liver cancer samples and found that the expression level of LAPTM4B was significantly higher in tumor tissues than that in paired nontumor tissues.2.We performed gain-and loss-of-function assays to investigate the effect of LAPTM4B on the proliferation of HCC cells.The results showed that LAPTM4B significantly promoted cell proliferation both in vivo and in vitro.3.The effects of LAPTM4B on autophagy in HCC cells were detected by western blot and immunofluorescence assay.The results showed that LAPTM4B could increase starvation-induced autophagy.4.qPCR and western blot assays were used to detect the ATGs expression following LAPTM4B overexpression and knockdown.The results showed that LAPTM4B could affect the expression of ATG3(autophagy related protein).Moreover,the expression of LAPTM4B was positively correlated with ATG3 in tumor tissues.5.LAPTM4B promotes autophagy through regulation of ATG3 in HCC.Silence of ATG3 abolished the promotion of autophagy induced by LAPTM4B upregulation,whereas overexpression of ATG3 rescued autophagy inhibition mediated by LAPTM4B silence.ConclusionLAPTM4B can not only increase the cell proliferation in HCC,but also induce autophagy of HCC.LAPTM4B promotes autophagy in an ATG3-dependent manner in HCC.