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LINC00163 inhibits the invasion and metastasis of gastric cancer cells as a ceRNA by sponging miR-183 to regulate the expression of AKAP12

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Abstract

Background

Gastric cancer (GC) is the most common and aggressive cancer of the digestive system and poses a serious threat to human health. Since genes do not work alone, our aim was to elucidate the potential network of mRNAs and noncoding RNAs (ncRNAs) in this study.

Methods

Transcriptome data of GC were obtained from TCGA. R and Perl were used to obtain the differentially expressed RNAs and construct a competing endogenous RNA (ceRNA) regulatory network. To investigate the biological functions of differentially expressed RNAs, loss-of-function and gain-of-function experiments were performed. Real-time PCR (RT-qPCR), western blot analysis, dual-luciferase reporter assays and fluorescence in situ hybridization were conducted to explore the underlying mechanisms of competitive endogenous RNAs (ceRNAs).

Results

Based on TCGA data and bioinformatics analysis, we identified the LINC00163/miR-183/A-Kinase Anchoring Protein 12 (AKAP12) axis. We observed that AKAP12 was weakly expressed in GC and suppressed invasion and metastasis in GC cells, which could be abolished by miR-183. In addition, LINC00163 can be used as a ceRNA to inhibit the expression of miR-183, thus enhancing the anticancer effect of AKAP12.

Conclusion

Our results demonstrated that weak LINC00163 expression in GC can sponge miR-183 to promote AKAP12. We established that the LINC00163/miR-183/AKAP12 axis plays an important role in GC invasion and metastasis and may be a potential biomarker and target for GC treatment.

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Funding

Liaoning S&T Project (20180550999), Shenyang young and middle-aged scientific & technological innovation talents support plan (RC180199).

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Authors and Affiliations

  1. Gastric Cancer Department, Liaoning Cancer Hospital and Institute (Cancer Hospital of China Medical University), No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning, China

    Jun Zhang, Shuai Guo, Yue Wang, Tao Zhang, Zhi-chao Zheng & Yan Zhao

  2. Medical Oncology Department of Gastrointestinal Cancer, Liaoning Cancer Hospital and Institute (Cancer Hospital of China Medical University), No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning, China

    Hai-yan Piao

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  1. Jun Zhang
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Contributions

JZ performed the majority of experiments and analyzed the data and drafted the manuscript; ZZ, YZ designed the research; SG conducted the molecular biology assays and assisted in writing the manuscript; YW collected and analyzed the data; TZ provided critical revision of the manuscript for important intellectual content.

Corresponding author

Correspondence to Yan Zhao.

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The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

The study was reviewed and approved by the Faculty of Science Ethics Committee at Liaoning Cancer Hospital and Institute (Cancer Hospital of China Medical University) (20181226).

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Supplementary file1 (DOCX 20 kb)

10147_2019_1604_MOESM2_ESM.pdf

Supplementary file2: Sup Figure 1 Differentially expressed RNAs in GC. A-C. Heatmaps of the expression levels of the top 50 differentially expressed lncRNAs (DELs), miRNAs (DEMis) and mRNAs (DEMs) screened by limma. D-F. Volcano plots of the expression levels of differentially expressed lncRNAs (DELs), miRNAs (DEMis) and mRNAs (DEMs) screened by limma. G-I. Principal component analysis (PCA) evaluates the screening of DELs, DEMis and DEMs by limma. J. The upregulated DELs identified by limma and edgeR. K. The downregulated DEMis identified by limma and edgeR. L. The upregulated DEMs identified by limma and edgeR (PDF 1780 kb)

10147_2019_1604_MOESM3_ESM.pdf

Supplementary file3: Sup Figure 2 A. The vector of AKAP12 upregulated the expression of AKAP12. B. The vector of LINC00163 upregulated the expression of LINC00163 (PDF 374 kb)

10147_2019_1604_MOESM4_ESM.pdf

Supplementary file4: Sup Figure 3 Effect of LINC00163, miR-183 and AKAP12 on cell proliferation. A, B. MiR-183 could promote the proliferation of GC, but AKAP12 had no effect on it. (A. SGC-7901, B. BGC-823). C, D. The inhibition of GC proliferation by LINC00163 could be reversed by overexpressed miR-183. (C. SGC-7901, D. BGC-823) (PDF 520 kb)

10147_2019_1604_MOESM5_ESM.pdf

Supplementary file5: Sup Figure 4 Effect of overexpression of miR-183 on AKAP12 expression and invasion and metastasis in GES-1. A, B. RT-PCR and western blot analyzed AKAP12 expression in GES-1 cells with the upregulated of miR-183. C, D. With the overexpression of miR-183, the migration ability of GES-1 increased (PDF 1986 kb)

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Zhang, J., Piao, Hy., Guo, S. et al. LINC00163 inhibits the invasion and metastasis of gastric cancer cells as a ceRNA by sponging miR-183 to regulate the expression of AKAP12. Int J Clin Oncol 25, 570–583 (2020). https://doi.org/10.1007/s10147-019-01604-w

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  • DOI: https://doi.org/10.1007/s10147-019-01604-w

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