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. 2017 Feb 28;116(5):626-633.
doi: 10.1038/bjc.2016.451. Epub 2017 Jan 12.

Circular RNA 0000096 affects cell growth and migration in gastric cancer

Peifei Li  1 , Huilin Chen  2 , Shengcan Chen  1 , Xiaoyan Mo  1 , Tianwen Li  1 , Bingxiu Xiao  1 , Rui Yu  1 , Junming Guo  1
Affiliations

Circular RNA 0000096 affects cell growth and migration in gastric cancer

Peifei Li et al. Br J Cancer. .

Retraction in

Abstract

Background: Circular RNAs (circRNAs) are a class of non-coding RNAs broadly expressed in cells of various species. Their role in cancers, especially in gastric cancer, is poorly understood.

Methods: Circular RNA 0000096 (hsa_circ_0000096) levels in 101 paired gastric cancer tissues and adjacent non-tumorous tissues from patients with gastric cancer were detected by real-time quantitative reverse transcription-polymerase chain reaction. A receiver operating characteristic curve was generated to evaluate the diagnostic value of hsa_circ_0000096. RNA interference was used to manipulate the expression of hsa_circ_0000096. Its biological effects were evaluated by flow cytometry, real-time cell analysis, a wound scratch assay, western blot analysis and xenograft models.

Results: Hsa_circ_0000096 was found to be significantly downregulated in gastric cancer tissues and gastric cancer cell lines compared with paired adjacent non-tumorous tissues and normal gastric epithelial cells (P<0.001). Moreover, knockdown of hsa_circ_0000096 significantly inhibited cell proliferation and migration in vitro and in vivo. The results of both immunohistochemical and western blot analyses showed that the protein levels of cyclin D1, cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-2 and MMP-9 were significantly reduced in vitro and in vivo. A gastric cancer xenograft nude mouse model indicated that Ki67 and VEGF were reduced in a dose-dependent manner following knockdown of hsa_circ_0000096. However, the expression of E-cadherin increased.

Conclusions: Hsa_circ_0000096 may be used as a potential novel biomarker for gastric cancer. It affects gastric cancer cell growth and migration by regulating cyclin D1, CDK6, MMP-2 and MMP-9.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The diagnostic value of hsa_circ_0000096 in gastric cancer. The expression of hsa_circ_0000096 was downregulated in gastric cancer tissues (A) and gastric cancer cells (B). The cutoff of hsa_circ_0000096 was 12.9 (C) and the area under the receiver operating characteristic (ROC) curve (AUC) was 0.82 (D). Data are presented as the mean±s.d., n=3. *P<0.05, **P<0.01, ***P<0.001.
Figure 2
Figure 2
Knockdown of hsa_circ_0000096 inhibits cell proliferation. Growth curves of the human normal gastric epithelial cell line GES-1 (A) and the human gastric cancer cell lines AGS (B), BGC-823 (C), HGC-27 (D), SGC-7901 (E) and MGC-803 (F) following knockdown of hsa_circ_0000096. Data are presented as the mean±s.d., n=3. NC, negative control. *P<0.05, **P<0.01, ***P<0.001.
Figure 3
Figure 3
Knockdown of hsa_circ_0000096 reduces cell migration ability. Cell migration in a human normal gastric epithelial cell line and human gastric cancer cell lines following knockdown of hsa_circ_0000096 (A, B). Representative wound scratch assay results (C). Data are presented as the mean±s.d., n=3. NC, negative control. *P<0.05, **P<0.01, ***P<0.001.
Figure 4
Figure 4
Expression levels of cell cycle-related and migration-related proteins in human normal gastric epithelial and human gastric cancer cell lines following knockdown of hsa_circ_0000096. Representative western blot results of cycle-related proteins cyclin D1 and CDK6 (A, B). Representative western blot results of migration-related proteins MMP-2 and MMP-9 (C, D). Data are presented as the mean±s.d., n=3. NC, negative control. *P<0.05, **P<0.01, ***P<0.001.
Figure 5
Figure 5
Transfection of siRNAs significantly inhibits tumour growth. The dose-dependent behaviour of hsa_circ_0000096 knockdown on BGC-823 (A) and MGC-803 (B) human gastric cancer cell lines. Data are presented as the mean±s.d., n=3. NC, negative control. *P<0.05, **P<0.01, ***P<0.001.
Figure 6
Figure 6
Knockdown of hsa_circ_0000096 suppresses cell cycle-related and migration-related protein expression. The results of cell cycle-related and migration-related protein levels in xenografts nude mouse models (A). Representative expression levels of cyclin D1, CDK6, MMP-2 and MMP-9 (B). Data are presented as the mean±s.d., n=3. NC, negative control. *P<0.05, **P<0.01, ***P<0.001.
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