Links between the oncoprotein YB-1 and small non-coding RNAs in breast cancer.
Links between the oncoprotein YB-1 and small non-coding RNAs in breast cancer.
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癌症YB-1与乳腺癌中小型非编码RNA之间的联系。
DOI：
10.1371/journal.pone.0080171
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lasham A
中科院分区：
文献类型：
--
作者：
Blenkiron C;Hurley DG;Fitzgerald S;Print CG;Lasham A
核酸结合蛋白YB-1是冷休克结构域蛋白家族的成员，与乳腺癌的进展有关，并与患者的不良生存有关。YB-1与另一个冷休克蛋白家族成员LIN28具有序列相似性，LIN28在包括microRNAs(MiRNAs)在内的小非编码RNA(SncRNAs)的调控中发挥作用。因此，为了研究YB-1和SncRNAs在乳腺癌中是否存在关联，我们研究了两种乳腺癌细胞系(腔A样细胞和基底细胞样细胞)中的SncRNAs是否与YB-1结合，以及SncRNAs和mRNAs的丰度是否随着YB-1表达的降低而改变。用抗YB-1抗体进行的RNA免疫沉淀表明，YB-1与几个SncRNAs结合。其中一些在两种乳腺癌细胞系中都与YB-1结合；另一些是细胞系特异性的。YB-1结合的小RNA来源于多种单链RNA家族，包括let-7和miR-320等miRNAs、转移RNAs、核糖体RNAs和小核仁RNAs(SnoRNA)。减少YB-1的表达改变了一些编码miRNA生物发生和加工蛋白的转录本的丰度，但不改变成熟或前体miRNAs的丰度。YB-1与特定的miRNAs、snoRNAs和tRNA衍生片段结合，似乎调节miRNA的生物发生和加工机制的表达。我们认为YB-1在乳腺癌中的一些致癌作用可能是通过它与SncRNAs的相互作用来实现的。
The nucleic acid-binding protein YB-1, a member of the cold-shock domain protein family, has been implicated in the progression of breast cancer and is associated with poor patient survival. YB-1 has sequence similarity to LIN28, another cold-shock protein family member, which has a role in the regulation of small noncoding RNAs (sncRNAs) including microRNAs (miRNAs). Therefore, to investigate whether there is an association between YB-1 and sncRNAs in breast cancer, we investigated whether sncRNAs were bound by YB-1 in two breast cancer cell lines (luminal A-like and basal cell-like), and whether the abundance of sncRNAs and mRNAs changed in response to experimental reduction of YB-1 expression. RNA-immunoprecipitation with an anti-YB-1 antibody showed that several sncRNAs are bound by YB-1. Some of these were bound by YB-1 in both breast cancer cell lines; others were cell-line specific. The small RNAs bound by YB-1 were derived from various sncRNA families including miRNAs such as let-7 and miR-320, transfer RNAs, ribosomal RNAs and small nucleolar RNAs (snoRNA). Reducing YB-1 expression altered the abundance of a number of transcripts encoding miRNA biogenesis and processing proteins but did not alter the abundance of mature or precursor miRNAs. YB-1 binds to specific miRNAs, snoRNAs and tRNA-derived fragments and appears to regulate the expression of miRNA biogenesis and processing machinery. We propose that some of the oncogenic effects of YB-1 in breast cancer may be mediated through its interactions with sncRNAs.
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影响因子：
8.4
作者：
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