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hsa-miR-17-92基因簇高度保守,可以作为抑癌基因抑制乳腺癌细胞的增殖.包括2个旁系同源体:miR-106a-363和miR-106b-25基因簇,其序列高度相似,可能通过调控共同靶基因而具有相似的功能.探讨3个基因簇转录的15条microRNA的序列特征,以及共调控靶基因在人类乳腺正常和癌细胞系中的表达;并进一步就显著差异表达基因进行GO和Pathway(KEGG)分析.结果表明,超过75%(178/236)的共调控靶基因表达具有显著差异性,这些基因可能与生物体的细胞代谢、转录后调控、生物合成等多种生物学过程有关,参与细胞周期,癌症等信号通路.分析发现乳腺特异基因PTPN4在乳腺癌中的低表达影响蛋白磷酸化水平和细胞周期,SMAD4、CCND1和E2F1作为与细胞周期相关基因在细胞的G1期起重要作用,它们的低表达阻止细胞从G1期进入S期,从而抑制癌细胞的生长,起到抑癌作用.特别是,一方面基因簇调控CCND1和E2F1使其低表达,另一方面它们作为转录因子结合到基因簇的启动子区诱导基因簇表达,从而形成负反馈调控循环调控下游基因表达.
The highly conserved hsa-miR-17-92 gene cluster can suppress the proliferation of breast cancer cells as a tumor suppressor gene and includes two paralogs, miR-106a-363 and miR-106b-25, whose sequence heights Similar to that may play a similar role by regulating common target genes.To investigate the sequence characteristics of fifteen microRNAs transcribed by three gene clusters and to co-regulate the expression of the target genes in normal human breast and cancer cell lines, and further significant differences The results of GO and Pathway (KEGG) analysis showed that over 75% (178/236) of co-regulatory target genes were significantly different, which may be related to the cellular metabolism, post-transcriptional regulation, biosynthesis and so on A variety of biological processes involved in cell cycle, cancer and other signaling pathways.It was found that low expression of breast specific gene PTPN4 in breast cancer affect protein phosphorylation and cell cycle, SMAD4, CCND1 and E2F1 as cell cycle related genes in G1 plays an important role in the cells, and their low expression prevents the cells from entering the S phase from the G1 phase, thus inhibiting the growth of cancer cells, play a tumor suppressor role.In particular, on the one hand the gene cluster regulation CCND1 and E2F1 Its low expression, on the other hand they bind to the transcription factor gene cluster promoter region of the gene cluster expression induced, thereby forming a negative feedback regulatory loop regulating gene expression downstream.