LOXL2 small molecule inhibitor restrains malignant transformation of cervical cancer cells by repressing LOXL2-induced epithelial-mesenchymal transition (EMT)
Lysyl oxidase-like 2 (LOXL2) is a member of the lysine oxidase (LOX) family. Although its overexpression is known to play pivotal roles in carcinogenesis, its involvement in cervical cancer remains undefined. Here, we comprehensively explored the expression level and functional mechanism of LOXL2 in cervical cancer using bioinformatics and experimental methods. Bioinformatics analysis revealed that LOXL2 was significantly upregulated in cervical cancer compared to normal tissues. 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, the small molecule inhibitor of LOXL2 ((2-Chloropyridin-4-yl) methanamine hydrochloride) significantly decreased the invasive ability of cervical cancer by reversing the process of LOXL2-induced EMT. In summary, LOXL2 may be a promising diagnostic and therapeutic biomarker for cervical cancer, and its small molecule inhibitor may be an effective anti-tumor drug.
基金:
National Key R&D Program of China [2021YFC2701201]; National Natural Science Foundation of China [82072895, 82141106, 82103134]; China Postdoctoral Science Foundation [2021M702223]; Shenzhen Science and Technology Innovation Commitiontee [JCYJ20210324105808022, RCBS20210706092345027]
第一作者单位:[1]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Canc Biol Res Ctr,Key Lab Minist Educ,Wuhan,Hubei,Peoples R China[2]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Dept Gynecol Oncol,Wuhan,Hubei,Peoples R China
通讯作者:
通讯机构:[1]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Canc Biol Res Ctr,Key Lab Minist Educ,Wuhan,Hubei,Peoples R China[2]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Dept Gynecol Oncol,Wuhan,Hubei,Peoples R China[4]Peking Univ, Dept Reprod Med, Shenzhen Hosp, Shenzhen, Guangdong, Peoples R China
推荐引用方式(GB/T 7714):
Peng Ting,Lin Shitong,Meng Yifan,et al.LOXL2 small molecule inhibitor restrains malignant transformation of cervical cancer cells by repressing LOXL2-induced epithelial-mesenchymal transition (EMT)[J].CELL CYCLE.2022,21(17):1827-1841.doi:10.1080/15384101.2022.2073047.
APA:
Peng, Ting,Lin, Shitong,Meng, Yifan,Gao, Peipei,Wu, Ping...&Wu, Peng.(2022).LOXL2 small molecule inhibitor restrains malignant transformation of cervical cancer cells by repressing LOXL2-induced epithelial-mesenchymal transition (EMT).CELL CYCLE,21,(17)
MLA:
Peng, Ting,et al."LOXL2 small molecule inhibitor restrains malignant transformation of cervical cancer cells by repressing LOXL2-induced epithelial-mesenchymal transition (EMT)".CELL CYCLE 21..17(2022):1827-1841