Ren Zhen-Hu, Shang Gao-Pan, Wu Kun, Hu Chuan-Yu, Ji Tong
Department of Oral and Maxillofacial & Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China.
Front Genet. 2020 Feb 14;11:39. doi: 10.3389/fgene.2020.00039. eCollection 2020.
Gastric cancer (GC) is one of the most common types of human cancers worldwide. However, the detail mechanisms underlying GC progression remained to be investigated. The present study identified 2823 differently expressed mRNAs and 441 differently expressed lncRNAs in GC. WGCNA was conducted to identify highly correlated lncRNAs and mRNAs. Bioinformatics analysis observed that these dysregulated lncRNAs were significantly associated with the regulation of angiogenesis, cell division, cell-cell adhesion, blood vessel development, adaptive immune response, gastric acid secretion, immune response. Co-expression analysis identified ILF3-AS1 was a key lncRNA involved in regulating GC progression. Loss of function assays showed that knockdown of ILF3-AS1 significantly suppressed GC cell proliferation and metastasis. Mechanically, the results indicate that ILF3-AS1 could enhance PTBP3 expression as an miR-29a sponge, thereby promoting the proliferation and metastasis of GC cells. Our work suggests that the ILF3-AS1/miR-29a/PTBP3 axis may be a potential target for the clinical diagnosis and treatment of GC.
胃癌(GC)是全球范围内最常见的人类癌症类型之一。然而,GC进展的具体机制仍有待研究。本研究在GC中鉴定出2823个差异表达的mRNA和441个差异表达的lncRNA。进行加权基因共表达网络分析(WGCNA)以鉴定高度相关的lncRNA和mRNA。生物信息学分析发现,这些失调的lncRNA与血管生成、细胞分裂、细胞间粘附、血管发育、适应性免疫反应、胃酸分泌、免疫反应的调节显著相关。共表达分析确定ILF3-AS1是参与调节GC进展的关键lncRNA。功能丧失实验表明,敲低ILF3-AS1可显著抑制GC细胞的增殖和转移。从机制上讲,结果表明ILF3-AS1可以作为miR-29a的海绵增强PTBP3的表达,从而促进GC细胞的增殖和转移。我们的工作表明,ILF3-AS1/miR-29a/PTBP3轴可能是GC临床诊断和治疗的潜在靶点。