转录因子RFX1上调FZD2促进乳腺癌增殖、侵袭和转移

RFX1-induced transcriptional activation of FZD2 accelerates the progression of breast cancer

目的探讨转录调节因子X1(RFX1)在乳腺癌中的表达及功能,探索其在乳腺癌中的调控机制。方法通过实时荧光定量PCR检测乳腺癌及配对乳腺癌旁组织中RFX1的相对表达量;通过生物信息学、染色质免疫沉淀技术(ChIP)和荧光素酶实验验证转录因子RFX1的靶基因;通过Western blot、CCK8、Transwell和划痕实验明确RFX1对乳腺癌增殖、侵袭、转移和上皮-间质转化(EMT)的影响。结果RFX1在乳腺癌组织中的表达高于癌旁正常组织(P<0.01),其表达水平与乳腺癌分期、类型和淋巴结转移状态有关(P<0.01)。体外实验结果表明RFX1促进乳腺癌细胞的增殖、迁移、转移和EMT过程,差异具有统计学意义(P<0.05)。生物信息学方法预测RFX1靶向调控FZD2,过表达RFX1使FZD2启动子区转录活性增强(P<0.01)。挽救实验提示外源性下调RFX1后乳腺癌细胞的增殖、侵袭、迁移和上皮-间质转化被FZD2逆转,差异具有统计学意义(P<0.05)。结论RFX1通过上调FZD2促进乳腺癌细胞的增殖、侵袭和转移。这一发现为乳腺癌的治疗提供了新的思路和靶点。

Objective To explore the expression and function of RFX1 and investigate its regulatory mechanism in breast cancer.Methods Real-time quantitative PCR was used to detect the relative expression level of RFX1 in cancer and adjacent tissues.Bioinformatics,CHIP,and luciferase experiments were performed to validate the target genes of transcription factor RFX1.Western blot,CCK8,Transwell,and wound healing assay were conducted to elucidate the effects of RFX1 on breast cancer proliferation,invasion,metastasis,and epithelial-mesenchymal transition(EMT).Results The expression of RFX1 in breast cancer tissues was found to be significantly higher than that in adjacent normal tissues(P<0.01).Furthermore,the expression level of RFX1 exhibited a significant correlation with breast cancer stage,type,and lymph node metastasis status(P<0.01).In vitro experiments revealed that RFX1 played a crucial role in promoting the proliferation,migration,metastasis,an d EMT process of breast cancer cells(P<0.05).Moreover,bioinformatics analysis predicted that RFX1 exerted its regulatory effects on the target gene FZD2.Overexpression of RFX1 was observed to enhance the transcriptional activity of the FZD2 promoter region(P<0.01).Subsequent rescue experiments demonstrated that the phenotypic changes associated with breast cancer,including proliferation,invasion,migration,and EMT,induced by RFX1 downregulation,which could be reversed by the involvement of FZD2(P<0.05).Conclusion RFX1 promotes breast cancer cell proliferation,invasion,and metastasis by upregulating FZD2.This finding provides new insights and targets for the treatment of breast cancer.