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长链非编码RNA FER1L4通过作为竞争性内源性RNA并调节PTEN表达来抑制癌细胞生长。

Long noncoding RNA FER1L4 suppresses cancer cell growth by acting as a competing endogenous RNA and regulating PTEN expression.

作者信息

Xia Tian, Chen Shengcan, Jiang Zhen, Shao Yongfu, Jiang Xiaoming, Li Peifei, Xiao Bingxiu, Guo Junming

机构信息

Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang, 315211, China.

出版信息

Sci Rep. 2015 Aug 26;5:13445. doi: 10.1038/srep13445.

Abstract

Aberrantly expressed long noncoding RNAs (lncRNAs) are associated with various cancers. However, the roles of lncRNAs in the pathogenesis of most cancers are unclear. Here, we report that the lncRNA FER1L4 (fer-1-like family member 4, pseudogene) acts as a competing endogenous RNA (ceRNA) to regulate the expression of PTEN (a well-known tumor suppressor gene) by taking up miR-106a-5p in gastric cancer. We observed that FER1L4 was downregulated in gastric cancer and that its level corresponded with that of PTEN mRNA. Both FER1L4 and PTEN mRNA were targets of miR-106a-5p. Further experiments demonstrated that FER1L4 downregulation liberates miR-106a-5p and decreases the abundances of PTEN mRNA and protein. More importantly, FER1L4 downregulation accelerated cell proliferation by promoting the G0/G1 to S phase transition. We conclude that one mechanism by which lncRNAs function in in tumorigenesis is as ceRNAs for tumor suppressor mRNAs.

摘要

异常表达的长链非编码RNA(lncRNA)与多种癌症相关。然而,lncRNA在大多数癌症发病机制中的作用尚不清楚。在此,我们报道lncRNA FER1L4(fer-1样家族成员4,假基因)在胃癌中作为一种竞争性内源RNA(ceRNA),通过结合miR-106a-5p来调节PTEN(一种著名的肿瘤抑制基因)的表达。我们观察到FER1L4在胃癌中表达下调,其水平与PTEN mRNA的水平相对应。FER1L4和PTEN mRNA均为miR-106a-5p的靶标。进一步实验表明,FER1L4下调会释放miR-106a-5p,并降低PTEN mRNA和蛋白质的丰度。更重要的是,FER1L4下调通过促进G0/G1期向S期转变加速细胞增殖。我们得出结论,lncRNA在肿瘤发生中发挥作用的一种机制是作为肿瘤抑制mRNA的ceRNA。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c1c/4549704/f472fd75325f/srep13445-f1.jpg

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