Differential expression of alternatively spliced transcripts related to energy metabolism in colorectal cancer.
Differential expression of alternatively spliced transcripts related to energy metabolism in colorectal cancer.
复制标题
与结直肠癌中能量代谢相关的剪接转录本的差异表达。
DOI：
10.1186/s12864-016-3351-5
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发表时间：
2016-12-28
期刊：
影响因子：
4.4
通讯作者：
Kudryavtseva AV
中科院分区：
文献类型：
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作者：
Snezhkina AV;Krasnov GS;Zaretsky AR;Zhavoronkov A;Nyushko KM;Moskalev AA;Karpova IY;Afremova AI;Lipatova AV;Kochetkov DV;Fedorova MS;Volchenko NN;Sadritdinova AF;Melnikova NV;Sidorov DV;Popov AY;Kalinin DV;Kaprin AD;Alekseev BY;Dmitriev AA;Kudryavtseva AV
结直肠癌（Colorectal cancer，CRC）是世界范围内最常见的恶性肿瘤之一。CRC的分子发病机制是异质性的，并且随后可能是癌基因和肿瘤抑制基因的突变、染色体和微卫星不稳定性、选择性剪接改变、CpG岛的超甲基化、氧化应激、不同信号传导途径和能量代谢的损伤。在本工作中，我们研究了CRC中与能量代谢相关的基因的选择性剪接模式的改变。使用CrossHub软件，我们分析了来自结肠肿瘤和匹配的正常组织的癌症基因组图谱（TCGA）RNA-Seq数据集。检测了参与细胞能量代谢的1014种替代mRNA亚型的表达。我们发现7个基因的差异表达的替代转录本，而这些基因的总体表达并没有显着改变，在CRC。已通过qPCR验证了一组8个差异表达的目标转录物。OGDH、COL 6A 3、ICAM 1、PHPT 1、PPP 2 R5 D、SLC 29 A1和Trib 3基因编码的这八种亚型在结直肠肿瘤中上调，这与生物信息学数据一致。COL 6A 3的替代转录物NM_057167在乳腺、肺、前列腺和肾肿瘤中也强烈上调。SLC 29 A1（NM_001078177）的选择性转录物仅在CRC样品中上调，但在其他测试的肿瘤类型中不上调。我们确定了在CRC中参与能量代谢的七个基因的可变剪接转录物的肿瘤特异性表达。我们的研究结果带来了关于结肠直肠癌中选择性剪接的新知识，并提出了一组可用于癌症诊断和治疗方法开发的mRNA亚型。本文的在线版本（doi：10.1186/s12864-016-3351-5）包含补充材料，可供授权用户使用。
Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. CRC molecular pathogenesis is heterogeneous and may be followed by mutations in oncogenes and tumor suppressor genes, chromosomal and microsatellite instability, alternative splicing alterations, hypermethylation of CpG islands, oxidative stress, impairment of different signaling pathways and energy metabolism. In the present work, we have studied the alterations of alternative splicing patterns of genes related to energy metabolism in CRC. Using CrossHub software, we analyzed The Cancer Genome Atlas (TCGA) RNA-Seq datasets derived from colon tumor and matched normal tissues. The expression of 1014 alternative mRNA isoforms involved in cell energy metabolism was examined. We found 7 genes with differentially expressed alternative transcripts whereas overall expression of these genes was not significantly altered in CRC. A set of 8 differentially expressed transcripts of interest has been validated by qPCR. These eight isoforms encoded by OGDH, COL6A3, ICAM1, PHPT1, PPP2R5D, SLC29A1, and TRIB3 genes were up-regulated in colorectal tumors, and this is in concordance with the bioinformatics data. The alternative transcript NM_057167 of COL6A3 was also strongly up-regulated in breast, lung, prostate, and kidney tumors. Alternative transcript of SLC29A1 (NM_001078177) was up-regulated only in CRC samples, but not in the other tested tumor types. We identified tumor-specific expression of alternative spliced transcripts of seven genes involved in energy metabolism in CRC. Our results bring new knowledge on alternative splicing in colorectal cancer and suggest a set of mRNA isoforms that could be used for cancer diagnosis and development of treatment methods. The online version of this article (doi:10.1186/s12864-016-3351-5) contains supplementary material, which is available to authorized users.