Gastric Cancer Department, Liaoning Cancer Hospital and Institute (Cancer Hospital of China Medical University), No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning, China.
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.
Int J Clin Oncol. 2020 Apr;25(4):570-583. doi: 10.1007/s10147-019-01604-w. Epub 2020 Jan 1.
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.
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).
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.
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.
胃癌（GC）是最常见和最具侵袭性的消化系统癌症，严重威胁人类健康。由于基因并非单独发挥作用，因此我们的目的是在本研究中阐明 mRNAs 和非编码 RNA（ncRNA）的潜在网络。
从 TCGA 中获取 GC 的转录组数据。使用 R 和 Perl 获得差异表达的 RNA 并构建竞争性内源性 RNA（ceRNA）调控网络。为了研究差异表达 RNA 的生物学功能，进行了功能丧失和功能获得实验。进行实时 PCR（RT-qPCR）、western blot 分析、双荧光素酶报告基因测定和荧光原位杂交，以探讨竞争性内源性 RNA（ceRNA）的潜在机制。
基于 TCGA 数据和生物信息学分析，我们确定了 LINC00163/miR-183/A-Kinase Anchoring Protein 12（AKAP12）轴。我们观察到 AKAP12 在 GC 中表达较弱，可抑制 GC 细胞的侵袭和转移，而 miR-183 可使其失活。此外，LINC00163 可作为 ceRNA 抑制 miR-183 的表达，从而增强 AKAP12 的抗癌作用。
我们的结果表明，GC 中较弱的 LINC00163 表达可以通过海绵吸附 miR-183 来促进 AKAP12。我们建立了 LINC00163/miR-183/AKAP12 轴在 GC 侵袭和转移中起重要作用，并且可能成为 GC 治疗的潜在生物标志物和靶标。
