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目的 通过生物信息学分析及实验验证,揭示长链非编码RNA PVT1在肿瘤中的表达及作用机制,为肿瘤的发病机制研究提供新的思路.方法 从starBase v2.0 公共数据库分析PVT1在14种常见肿瘤中的表达,利用PVT1 RNA原位杂交实验验证PVT1在肿瘤中的表达方式.运用UCSC Genome Browser、HMDD v2.0、miRTar Base、JASPAR等数据库对长链非编码RNA PVT1的上游转录因子、下游靶microRNA及靶基因进行生物信息学预测及分析,并进一步推导其分子调控通路.结果 通过starBase数据库分析及RNA原位杂交实验验证,PVT1在肾透明细胞癌和结直肠癌中高表达.PVT1受上游CREB1、Atf1、SP1、KLF5、STAT3等转录因子的调控;PVT1能与miR-16特异性结合并调控其表达, miR-16的靶基因bcl-2、VEGFA、CCNE1、CCND1、SHOC2与PVT1的转录因子存在相互作用,形成一个反馈调控通路.结论 PVT1在肾透明细胞癌及结直肠癌中高表达,生物信息学预测分析显示转录因子/PVT1/miR-16/靶基因信号轴可能是肾癌及结直肠癌的重要分子机制,为进一步研究长链非编码RNA功能机制提供新思路.

Objective To study the expression and mechanism of long-chain non-coding RNA PVT1 in tumor by bioinformatics analysis and experimental verification, and to provide new ideas for the study of the pathogenesis of tumors.Methods The expression of PVT1 in 14 common tumors was downloaded from starBase v2.0 public database, which also was verified by PVT1 RNA-in situ hybridization.The upstream transcription factors,the downstream target microRNA(miRNA) for PVT1 and the target genes for the target miRNAs were predicted and analyzed by using bioinformatics based on the database of UCSC Genome Browser,HMDD v2.0,miRTar Base, JASPAR databases. Results StarBase database analysis and RNA in situ hybridization showed that PVT1 was highly expressed in kidney clear cell carcinoma and colon and rectal adenocarcinoma.PVT1 was regulated by the upstream transcription factors CREB1,Atf1,SP1,KLF5,STAT3,while it could control the expression of the downstream target miR-16. bcl-2,VEGFA,CCNE1,CCND1 and SHOC2 showed an interaction with the transcription factor of PVT1,which formed a feedback regulatory pathway.Conclusions PVT1 is highly expressed in kidney clear cell carcinoma and colon and rectal adenocarcinoma.The predictive analysis of bioinformatics demonstrates that transcription factor/PVT1/miR-16/target gene signal axon may be an important molecular mechanism,which provide a valuable clue for further functional mechanism research of long-chain non-coding RNA.