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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.
International Journal of Clinical Oncology ( IF 3.3 ) Pub Date : 2020-01-01 , DOI: 10.1007/s10147-019-01604-w
Jun Zhang 1 , Hai-Yan Piao 2 , Shuai Guo 1 , Yue Wang 1 , Tao Zhang 1 , Zhi-Chao Zheng 1 , Yan Zhao 1
Affiliation  

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.

中文翻译:

LINC00163通过使miR-183海绵化以调节AKAP12的表达,以ceRNA的形式抑制胃癌细胞的侵袭和转移。

背景技术胃癌(GC)是消化系统的最常见和侵袭性癌症,并且对人类健康构成严重威胁。由于基因不能单独起作用,因此我们的目的是阐明这项研究中潜在的mRNA和非编码RNA(ncRNA)网络。方法从TCGA获得GC的转录组数据。R和Perl用于获得差异表达的RNA,并构建竞争性内源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。进行了实时PCR(RT-qPCR),蛋白质印迹分析,双荧光素酶报告基因分析和荧光原位杂交,以探索竞争性内源RNA(ceRNA)的潜在机制。结果基于TCGA数据和生物信息学分析,我们确定了LINC00163 / miR-183 / A激酶锚定蛋白12(AKAP12)轴。我们观察到AKAP12在GC中表达较弱,并抑制了GC细胞中的侵袭和转移,这可能被miR-183所废除。此外,LINC00163可以用作ceRNA来抑制miR-183的表达,从而增强AKAP12的抗癌作用。结论我们的结果表明,GC中的弱LINC00163表达可以抑制miR-183促进AKAP12。我们确定LINC00163 / miR-183 / AKAP12轴在GC的侵袭和转移中起着重要作用,并且可能是潜在的生物标志物和GC治疗的靶标。我们观察到AKAP12在GC中表达较弱,并抑制了GC细胞中的侵袭和转移,这可能被miR-183所废除。此外,LINC00163可以用作ceRNA来抑制miR-183的表达,从而增强AKAP12的抗癌作用。结论我们的结果表明,GC中弱的LINC00163表达可以使miR-183促进AKAP12。我们确定LINC00163 / miR-183 / AKAP12轴在GC的侵袭和转移中起着重要作用,并且可能是潜在的生物标志物和GC治疗的靶标。我们观察到AKAP12在GC中表达较弱,并抑制了GC细胞中的侵袭和转移,这可能被miR-183所废除。另外,LINC00163可以用作ceRNA来抑制miR-183的表达,从而增强AKAP12的抗癌作用。结论我们的结果表明,GC中弱的LINC00163表达可以使miR-183促进AKAP12。我们确定LINC00163 / miR-183 / AKAP12轴在GC的侵袭和转移中起着重要作用,并且可能是潜在的生物标志物和GC治疗的靶标。结论我们的结果表明,GC中弱的LINC00163表达可以使miR-183促进AKAP12。我们确定LINC00163 / miR-183 / AKAP12轴在GC的侵袭和转移中起着重要作用,并且可能是潜在的生物标志物和GC治疗的靶标。结论我们的结果表明,GC中弱的LINC00163表达可以使miR-183促进AKAP12。我们确定LINC00163 / miR-183 / AKAP12轴在GC的侵袭和转移中起着重要作用,并且可能是潜在的生物标志物和GC治疗的靶标。
更新日期:2020-01-04
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