Abstract：
The cytochrome P450s (CYP450s) include key oxidative enzymes involved in the metabolism of various carcinogens and anticancer drugs. Bioinformatic studies have demonstrated the association of CYP3A43 with liver cancer and ovarian cancer. However, the biological function of CYP3A43 in tumor progression remains unclear. To further reveal the role of CYP3A43 in tumor progression, we first analyzed the data from the UALCAN database and found that CYP3A43 was negatively correlated to the cancer staging and lymph node metastasis of lung adenocarcinoma (LUAD). We established stable CYP3A43-knockdown LUAD H1299 cell line and found that its knockdown enhanced cell proliferation, colony formation, and migration in vitro, and promoted the growth of tumor xenograft in vivo. Interestingly, when CYP3A43 was ectopically-expressed in the LUAD cell lines, decreased cell proliferation and ERK1/2 phosphorylation level were observed. Lastly, we also identified CYP3A43 co-expressed genes in LUAD from LinkedOmics database followed by GO and KEGG analyses. In conclusion, our results indicate the unprecedented role of CYP3A43 in the suppression of LUAD and provide new possibilities for targeted therapy of this life-threatening disease.
摘要：
细胞色素P450(CYP450)包括参与各种致癌物和抗癌药物代谢的关键氧化酶。生物信息学研究已经证明CYP3A43与肝癌和卵巢癌的相关性。然而,CYP3A43在肿瘤进展中的生物学功能尚不清楚。为了进一步揭示CYP3A43在肿瘤进展中的作用，我们首先分析了UALCAN数据库的数据,发现CYP3A43与肺腺癌(LUAD)的癌症分期和淋巴结转移呈负相关.我们建立了稳定的CYP3A43敲低LUADH1299细胞系，发现其敲低可增强细胞增殖，菌落形成,和体外迁移，促进了体内移植瘤的生长。有趣的是,当CYP3A43在LUAD细胞系中异位表达时，观察到细胞增殖和ERK1/2磷酸化水平降低。最后,我们还从LinkedOmics数据库中鉴定了LUAD中CYP3A43共表达的基因,随后进行了GO和KEGG分析.总之,我们的结果表明CYP3A43在抑制LUAD方面发挥了前所未有的作用,并为靶向治疗这种危及生命的疾病提供了新的可能性.
