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在胃癌细胞中选择长链非编码RNA用于生物活性肽和化疗药物的定向治疗。

Selecting lncRNAs in gastric cancer cells for directed therapy with bioactive peptides and chemotherapy drugs.

作者信息

Han Wenyan, Xiao Rui, Zhang Chuanling, Suyila Qimuge, Li Xian, Su Xiulan

机构信息

Clinical Medical Research Center of The Affiliated Hospital, Inner Mongolia Medical University, Hohhot 010050, Inner Mongolia Autonomous Region, P.R. China.

Inner Mongolia Key Laboratory of Molecular Pathology, Inner Mongolia Medical University, Huhhot 010059, Inner Mongolia Autonomous Region, P.R. China.

出版信息

Oncotarget. 2017 Sep 18;8(49):86082-86097. doi: 10.18632/oncotarget.20977. eCollection 2017 Oct 17.

Abstract

Selecting lncRNAs for directed therapy with bioactive peptides and chemotherapy drugs may be an effective approach to treating gastric cancer (GC). We show genome-scale identification and characterization of differentially expressed lncRNAs in GC cells treated with a novel anti-cancer bioactive peptide (ACBP) and the chemotherapy drug oxaliplatin (ASLB). A total of 17,897 lncRNAs were identified through pairwise comparison, including 2,074 novel lncRNAs. Of those, 1,386 lncRNAs were differentially expressed (over 1.5-fold change vs. control, value < 0.05) in response to ACBP and ASLB treatment. These included 914 upregulated and 472 downregulated lincRNAs. Functional annotation of these lncRNAs through Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis revealed they activate metabolic pathways and protein-binding processes. Moreover, suppression of the DNA replication process and upregulation of AMP-activated protein kinase (AMPK) signaling in MKN45 cells exposed to ACBP alone or in combination with ASLB was predicted by hierarchical clustering analysis. By providing new insight into the transcriptomic effects of ACBP and ASLB in GC cells, these results provide the first evidence of ACBP inhibition of lincRNAs and may provide new mechanisms of action for ACBP and ASLB.

摘要

选择lncRNAs用于生物活性肽和化疗药物的定向治疗可能是治疗胃癌(GC)的有效方法。我们展示了在经新型抗癌生物活性肽(ACBP)和化疗药物奥沙利铂(ASLB)处理的GC细胞中差异表达lncRNAs的全基因组规模鉴定和表征。通过成对比较共鉴定出17,897个lncRNAs,其中包括2,074个新型lncRNAs。在这些lncRNAs中,有1,386个lncRNAs在ACBP和ASLB处理后差异表达(与对照相比变化超过1.5倍,值<0.05)。其中包括914个上调和472个下调的长链非编码RNA(lincRNAs)。通过京都基因与基因组百科全书(KEGG)通路分析对这些lncRNAs进行功能注释,发现它们激活代谢途径和蛋白质结合过程。此外,通过层次聚类分析预测,单独暴露于ACBP或与ASLB联合处理的MKN45细胞中,DNA复制过程受到抑制,AMP激活的蛋白激酶(AMPK)信号上调。通过对ACBP和ASLB在GC细胞中的转录组效应提供新的见解,这些结果首次证明了ACBP对lincRNAs的抑制作用,并可能为ACBP和ASLB提供新的作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a6c/5689669/f7dd4b71fa15/oncotarget-08-86082-g001.jpg

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