Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041, China.
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
Int J Mol Sci. 2022 Dec 21;24(1):113. doi: 10.3390/ijms24010113.
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.
细胞色素 P450s（CYP450s）包括参与各种致癌物质和抗癌药物代谢的关键氧化酶。生物信息学研究表明 CYP3A43 与肝癌和卵巢癌有关。然而，CYP3A43 在肿瘤进展中的生物学功能仍不清楚。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 数据库中的数据，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 LUAD H1299 细胞系，发现其敲低可增强细胞在体外的增殖、集落形成和迁移，并促进肿瘤异种移植物在体内的生长。有趣的是，当 CYP3A43 在 LUAD 细胞系中外源表达时，观察到细胞增殖减少和 ERK1/2 磷酸化水平降低。最后，我们还从 LinkedOmics 数据库中鉴定了 LUAD 中的 CYP3A43 共表达基因，随后进行了 GO 和 KEGG 分析。总之，我们的结果表明 CYP3A43 在抑制 LUAD 方面具有前所未有的作用，并为这种危及生命的疾病的靶向治疗提供了新的可能性。
