目的：探讨碱性核蛋白1（BNC1）对食管鳞状细胞癌（ESCC）细胞增殖、迁移、侵袭、细胞周期和凋亡的影响及其作用机制。方法：通过qPCR法检测ESCC细胞和正常食管上皮细胞中BNC1 mRNA的表达水平，免疫组织化学染色法检测10例ESCC患者癌及癌旁组织中BNC1的蛋白表达水平。利用siRNA敲低BNC1在KYSE-150和KYSE-30细胞中的表达，CCK-8法、划痕愈合实验、Transwell实验和流式细胞术检测BNC1对细胞增殖、迁移、侵袭、细胞周期和凋亡等的影响。通过CHIP-seq实验和GEPIA在线网站数据分析并结合敲低BNC1后的转录组测序数据分析筛选BNC1调控的下游靶基因，qPCR法验证BNC1敲低后靶基因的表达变化，并用双荧光素酶报告基因实验验证BNC1对靶基因的调控作用。结果：BNC1 mRNA和蛋白水平在ESCC组织中较癌旁组织高表达（均P<0.01）。敲低BNC1可明显抑制KYSE-150、KYSE-30细胞的增殖、迁移和侵袭能力（P<0.05或P<0.01），将细胞阻滞于G1期并促进细胞的凋亡（均P<0.01）。CHIP-seq实验结果和在线网站GEPIA数据分析结合敲低BNC1后的转录组测序数据显示，G蛋白通路抑制因子1（GPS1）可能为BNC1正向调控的致癌靶基因。qPCR法和双荧光素酶报告基因实验结果显示，BNC1对GPS1有调控作用（P<0.01）。结论：BNC1在ESCC组织和细胞中高表达，干扰BNC1可显著抑制ESCC细胞的增殖、迁移和侵袭能力，阻滞细胞于G1期并促进细胞凋亡，其机制可能是BNC1通过靶向GPS1调控ESCC细胞的恶性生物学行为。

Objective: To investigate the effects of basonuclin 1 (BNC1) on the proliferation, migration, invasion, cell cycle and apoptosis of esophageal squamous cell carcinoma (ESCC) cells and its mechanism. Methods: TThe mRNA expression level of BNC1 in ESCC cells and normal esophageal epithelial cells was detected by qPCR. The protein expression level of BNC1 in cancer and para-cancerous tissues of 10 ESCC patients was detected by immunohistochemical staining. The expression of BNC1 in KYSE-150 and KYSE-30 cells was down-regulated by siRNA, and the effects of BNC1 on cell proliferation, migration, invasion, cell cycle andapoptosis were investigated using CCK-8, scratch healing, Transwell and flow cytometry assays, respectively. The downstream targetgenes of BNC1 were identified by ChIP-seq assay and GEPIA online website date analysis combined with knockdown transcriptome sequencing data after BNC1 knockdown. qPCR was used to verify the expression of target genes after BNC1 knockdown, and dualluciferase reporter gene assay was used to confirm the regulatory effect of BNC1 on the target genes. Results:The mRNA and protein levels of BNC1 were higher in ESCC tissues than in para-cancerous tissues (all P<0.01). Knockdown of BNC1 significantly inhibited the proliferation, migration and invasion of KYSE-150 and KYSE-30 cells (P<0.01 or P<0.01), arrested the cells in G1 phase and promoted the cell apoptosis (all P<0.01). The results of ChIP-seq assay and online website GEPIA date analysis combined with at transcriptome sequencing data indicated after BNC1 knockdown that G protein pathway repressor 1 (GPS1) may be a oncogenic target gene that positively regulated by BNC1. The results of qPCR and dual luciferase reporter gene assay showed that BNC1 had a regulatory effect on GPS1 (P<0.01). Conclusion: BNC1 is highly expressed in ESCC tissues and cells. Interfering with BNC1 significantly inhibits the proliferation, migration and invasion of ESCC cells, arrests cells at G1 phase and promotes cell apoptosis possibly by targeting GPS1 to regulate the malignant biological behaviors of ESCC cells.

四川省卫生健康委员会科研资助项目（No. 20PJ177）；南充市市校科技战略合作项目（No. 20SXQT0328，No. 20SXPTJS0003）