Yan Yichao, Shen Zhanlong, Gao Zhidong, Cao Jian, Yang Yang, Wang Bo, Shen Chao, Mao Shuqiang, Jiang Kewei, Ye Yingjiang, Wang Shan
Departments of Gastroenterological Surgery and Surgical Oncology, Peking University People's Hospital, Beijing, China.
J Gastroenterol Hepatol. 2015 Sep;30(9):1367-75. doi: 10.1111/jgh.12976.
Increasing evidence has indicated that long noncoding ribonucleic acids (lncRNAs) play a major role in cancers. Although certain lncRNAs has been reported to play a role in gastric cancer (GC), specific lncRNAs involved in distant metastasis of GC remain unknown.
Differentially expressed mRNAs and lncRNAs between stage IV and non-stage IV GC were obtained by microarray. Gene ontology and pathway analysis were used to study functions of differential mRNAs. Algorithms were used to predict potential gene targets of cis or trans-acting lncRNAs. Network analysis was performed to analyze each pair of gene-lncRNA, gene-gene, or lncRNA-lncRNA interactions. Expression of lncRNA special for distant metastasis of GC (SDMGC) and target gene TRIM16 were tested in GC tissues and cell lines. RNAi and overexpression were used to observe the biological functions of SDMGC and TRIM16 on GC cells.
502 mRNAs and 440 lncRNAs were found to be differentially expressed. 74 gene ontology terms and 38 pathways were associated with the dysregulated transcripts. Fourteen core factors were determined by network analysis. Expression of SDMGC and TRIM16 was upregulated in the distant metastasis tissues, compared with primary GC tissues, which were positive correlation. Silencing of SDMGC or TRIM16 was demonstrated to decrease cell invasion and migration, while upregulated of SDMGC or TRIM16 could promote cell invasion and migration. However, little effect on proliferation, cell cycle, colony formation, and apoptosis was found.
SDMGC is obviously upregulated in stage IV GC and may represent a new marker and therapeutic target for GC treatment.
越来越多的证据表明长链非编码核糖核酸（lncRNAs）在癌症中起主要作用。尽管已有报道某些lncRNAs在胃癌（GC）中发挥作用，但参与GC远处转移的特定lncRNAs仍不清楚。
通过微阵列获得IV期和非IV期GC之间差异表达的mRNA和lncRNAs。基因本体论和通路分析用于研究差异mRNA的功能。使用算法预测顺式或反式作用lncRNAs的潜在基因靶点。进行网络分析以分析每对基因-lncRNA、基因-基因或lncRNA-lncRNA相互作用。在GC组织和细胞系中检测GC远处转移特异性lncRNA（SDMGC）和靶基因TRIM16的表达。使用RNA干扰和过表达来观察SDMGC和TRIM16对GC细胞的生物学功能。
发现502个mRNA和440个lncRNAs差异表达。74个基因本体学术语和38条通路与失调的转录本相关。通过网络分析确定了14个核心因子。与原发性GC组织相比，SDMGC和TRIM16在远处转移组织中的表达上调，二者呈正相关。SDMGC或TRIM16的沉默可降低细胞侵袭和迁移，而SDMGC或TRIM16的上调可促进细胞侵袭和迁移。然而，对增殖、细胞周期、集落形成和凋亡几乎没有影响。
SDMGC在IV期GC中明显上调，可能代表GC治疗的新标志物和治疗靶点。
