LOXL2 Small Molecule Inhibitor Restrains Malignance Of Cervical Cancer Cells By Reversing Epithelial-mesenchymal Transition (EMT)

Objective: Cervical cancer is a common malignant disease threatening women’s life and health in developing countries.Lysyl oxidase-like 2(LOXL2)is a member of the lysine oxidase(LOX)family,and its overexpression is known to play a pivotal role in carcinogenesis.However,its involvement in cervical cancer remains undefined.Here,we aimed to explore the role of LOXL2 in cervical cancer,and the therapeutic effect of LOXL2 small molecule inhibitor((2-chloropyridine-4-yl)formamide hydrochloride)on cervical cancer using bioinformatics and experimental methods.Materials and methods: We used online databases(e.g.,ONCOMINE,COSMIC,Linked Omics,Kaplan-Meier Plotter)to explore the expression level and prognostic value of LOXL2 in cervical cancer,and further determine the role of LOXL2 in cervical cancer.Furthermore,we identified the effects of LOXL2 and its small molecule inhibitor in vitro(invasion,migration,colony formation,scratch,etc.)and in vivo(xenograft model)on cervical cancer cell lines(SIHA and HELA).Results: Bioinformatics analysis revealed that LOXL2 was significantly up-regulated in cervical cancer compared to normal tissues.Over-expression of LOXL2 was significantly correlated with poor survival(e.g.,overall survival,progression-free survival)in cervical cancer.Functional enrichment analysis showed that most positively or negatively correlated genes of LOXL2 were correlated with extracellular matrix(ECM)formation and epithelial-mesenchymal transition(EMT).Further experiments confirmed that overexpression of LOXL2 greatly enhanced the malignant transformation abilities(e.g.,proliferation,invasion,and migration)of cervical cancer cells via mediation of EMT.Furthermore,we verified that the small molecule inhibitor of LOXL2 significantly decreased the invasive ability of cervical cancer by reversing the process of LOXL2-induced EMT in vitro and in vivo levels.Conclusions: In summary,LOXL2 may be a promising diagnostic and therapeutic biomarker for cervical cancer,and its small molecule inhibitor can reverse LOXL2 mediated EMT,which may be an effective anti-tumor drug for cervical cancer.