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. 2015 Aug 26:5:13445.
doi: 10.1038/srep13445.

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

Tian Xia  1 , Shengcan Chen  1 , Zhen Jiang  1 , Yongfu Shao  1 , Xiaoming Jiang  1 , Peifei Li  1 , Bingxiu Xiao  1 , Junming Guo  1   1
Affiliations

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

Tian Xia et al. Sci Rep. .

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.

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Figures

Figure 1
Figure 1. Expression of FER1L4 in gastric cancer cells and tissues.
(a) Expression of FER1L4 in a human normal gastric epithelial cell line and human gastric cancer cell lines. Data are presented as mean ± SD, n = 3. **P < 0.01, ***P < 0.001. Expression of FER1L4 (b) and PTEN (c) in the “FER1L4 high” and “FER1L4 low” subsets. n = 10, *P < 0.05.
Figure 2
Figure 2. Expression of FER1L4 and PTEN in a human normal gastric epithelial cell line and human gastric cancer cell lines transfected with miR-106a-5p mimics (a,b) or inhibitors (c).
Data are presented as mean ± SD, n = 3. NC, negative control. *P < 0.05, **P < 0.01, ***P < 0.001.
Figure 3
Figure 3. miR-106a-5p levels in a human normal gastric epithelial cell line and human gastric cancer cell lines after FER1L4 knockdown.
(a) transfection efficiency. Scale bars, 500 μm. (b) Data are presented as mean ± SD, n = 3. NC, negative control. *P < 0.05, ***P < 0.001.
Figure 4
Figure 4. Expression of PTEN in a human normal gastric epithelial cell line and human gastric cancer cell lines after FER1L4 knockdown.
(a) PTEN mRNA levels detected by qRT-PCR. Data are presented as mean ± SD, n = 3. NC, negative control. *P < 0.05, **P < 0.01. (b) Representative cropped results of Western blot analyses. (c) Results of Western blot analyses of three independent experiments. NC, negative control. **P < 0.01, ***P < 0.001. The gels were run under the same experimental conditions. The blots were processed in parallel.
Figure 5
Figure 5. Cell cycle distributions in a human normal gastric epithelial cell line and human gastric cancer cell lines following FER1L4 knockdown.
(a) Representative original flow cytometry results. (b) Data are presented as mean ± SD, n = 3. NC, negative control. *P < 0.05, **P < 0.01, ***P < 0.001.
Figure 6
Figure 6. Growth curves of the human normal gastric epithelial cell line GES-1 (a) and the human gastric cancer cell lines AGS (b), MGC-803 (c) and SGC-7901 (d) following FER1L4 knockdown.
Data are presented as mean ± SD, n = 3. NC, negative control. *P < 0.05, **P < 0.01, ***P < 0.001.
Figure 7
Figure 7. ceRNA networks associated with PTEN.
See this image and copyright information in PMC

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