| Recent evidence indicates that long non-coding RNAs(lncRNAs)play a critical role in the regulation of cellular processes such as differentiation,proliferation,and metastasis.These lncRNAs are dysregulated in a variety of cancers including gastric cancer.In this study,we analyzed gastric cancer-normal microarray data from GEO dataset and found that lncRNA HOTTIP expression was significantly up-regulated in gastric cancer tissues when compared with normal tissues.HOTTIP gene is located at human HOXA locus(7p15.2)and is an 4665nt-long antisense transcript lncRNA.Furthermore,qPCR results showed that HOTTIP expression is also up-regulated in gastric cancer cells.Bioinfomatics analysis showed that there are E2F1 and SP1 binding sites reside in the HOTTIP promoter region,and ChIP assays indicated that E2F1 and SP1 involves in upregulating HOTTIP transcription in gastric cancer cells.Knockdown of HOTTIP could inhibit gastric cancer cells proliferation and promote gastric cancer cells apoptosis both in vitro and in vivo.Moreover,Functional genomic analysis of RNA-sequencing results showed that knockdown of HOTTIP could affect lots of genes expression that contribute to cell development and apoptosis regulation.By using bioinfomatic analysis,we found HOXA13 and BTG2 were two promising downstream of HOTTIP.Meanwhile,it is the first time to evaluate function of HOXA13 in gastric cancer.Further mechanism research indicated that HOTTIP could bind PRC2 in gastric cancer cells,which proved to be mediator of HOTTIP regulating BTG2 expression.Of most relevance,translation of these findings into human gastric cancer tissue samples using bioinformatics demonstrated that HOTTIP expression positively correlated with genes that upregulated in early gastric cancer and negatively correlated with genes involved in apoptosis pathway,suggesting that HOTTIP could be a biomarker for carcinogenesis of gastric cancer. |
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