Jing Fangyuan, Jin Huicheng, Mao Yingying, Li Yingjun, Ding Ye, Fan Chunhong, Chen Kun
1 Department of Epidemiology and Biostatistics, Zhejiang University School of Public Health, Hangzhou, China.
2 Department of Public Health, Hangzhou Medical College, Hangzhou, China.
Tumour Biol. 2017 May;39(5):1010428317703650. doi: 10.1177/1010428317703650.
Long non-coding RNAs (lncRNAs) are widely transcribed in the genome, but their expression profile and roles in colorectal cancer are not well understood. The aim of this study was to investigate the long non-coding RNA expression profile in colorectal cancer and look for potential diagnostic biomarkers of colorectal cancer. Long non-coding RNA microarray was applied to investigate the global long non-coding RNA expression profile in colorectal cancer. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed using standard enrichment computational methods. The expression levels of selected long non-coding RNAs were validated by quantitative reverse transcription polymerase chain reaction. The relationship between long non-coding RNA expression levels and clinicopathological characteristics of colorectal cancer patients was assessed. Coexpression analyses were carried out to find the coexpressed genes of differentially expressed long non-coding RNAs, followed by gene ontology analysis to predict the possible role of the selected long non-coding RNAs in colorectal carcinogenesis. In this study, a total of 1596 long non-coding RNA transcripts and 1866 messenger RNA transcripts were dysregulated in tumor tissues compared with paired normal tissues. The top upregulated long non-coding RNAs in tumor tissues were CCAT1, UCA1, RP5-881L22.5, NOS2P3, and BC005081 and the top downregulated long non-coding RNAs were AK055386, AC078941.1, RP4-800J21.3, RP11-628E19.3, and RP11-384P7.7. Long non-coding RNA UCA1 was significantly upregulated in colon cancer, and AK055386 was significantly downregulated in tumor with dimension <5 cm. Functional prediction analyses showed that both the long non-coding RNAs coexpress with cell cycle related messenger RNAs. The current long non-coding RNA study provided novel insights into expression profile in colorectal cancer and predicted the potential roles of long non-coding RNAs in colorectal carcinogenesis. Among the dysregulated long non-coding RNAs, UCA1 was found to be associated with anatomic site, and AK055386 was found associated with tumor size. Further functional investigations into the molecular mechanisms are warranted to clarify the role of long non-coding RNA in colorectal carcinogenesis.
长链非编码RNA（lncRNAs）在基因组中广泛转录，但其在结直肠癌中的表达谱及作用尚未完全明确。本研究旨在探究结直肠癌中长链非编码RNA的表达谱，并寻找结直肠癌潜在的诊断生物标志物。应用长链非编码RNA微阵列技术研究结直肠癌中整体长链非编码RNA的表达谱。采用标准富集计算方法进行基因本体论（Gene ontology）和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes）通路分析。通过定量逆转录聚合酶链反应验证所选长链非编码RNA的表达水平。评估长链非编码RNA表达水平与结直肠癌患者临床病理特征之间的关系。进行共表达分析以寻找差异表达长链非编码RNA的共表达基因，随后进行基因本体论分析以预测所选长链非编码RNA在结直肠癌发生中的可能作用。在本研究中，与配对的正常组织相比，肿瘤组织中共有1596个长链非编码RNA转录本和1866个信使RNA转录本表达失调。肿瘤组织中上调最明显的长链非编码RNA为CCAT1、UCA1、RP5 - 881L22.5、NOS2P3和BC005081，下调最明显的长链非编码RNA为AK055386、AC078941.1、RP4 - 800J21.3、RP11 - 628E19.3和RP11 - 384P7.7。长链非编码RNA UCA1在结肠癌中显著上调，AK055386在肿瘤直径<5 cm的肿瘤中显著下调。功能预测分析表明，这两种长链非编码RNA均与细胞周期相关信使RNA共表达。目前的长链非编码RNA研究为结直肠癌的表达谱提供了新的见解，并预测了长链非编码RNA在结直肠癌发生中的潜在作用。在表达失调的长链非编码RNA中，发现UCA1与解剖部位有关，AK055386与肿瘤大小有关。有必要对分子机制进行进一步的功能研究，以阐明长链非编码RNA在结直肠癌发生中的作用。
