Department of Animal Science, University of Tehran, Karaj, Iran.
PLoS One. 2011;6(11):e27118. doi: 10.1371/journal.pone.0027118. Epub 2011 Nov 4.
Tandem repeats are found in both coding and non-coding sequences of higher organisms. These sequences can be used in cancer genetics and diagnosis to unravel the genetic basis of tumor formation and progression. In this study, a possible relationship between SSR distributions and lung cancer was studied by comparative analysis of EST-SSRs in normal and lung cancerous tissues. While the EST-SSR distribution was similar between tumorous tissues, this distribution was different between normal and tumorous tissues. Trinucleotides tandem repeats were highly different; the number of trinucleotides in ESTs of lung cancer was 3 times higher than normal tissue. Significant negative correlation between normal and cancerous tissue showed that cancerous tissue generates different types of trinucleotides. GGC and CGC were the more frequent expressed trinucleotides in cancerous tissue, but these SSRs were not expressed in normal tissue. Similar to the EST level, the expression pattern of EST-SSRs-derived amino acids was significantly different between normal and cancerous tissues. Arg, Pro, Ser, Gly, and Lys were the most abundant amino acids in cancerous tissues, and Leu, Cys, Phe, and His were significantly more abundant in normal tissues than in cancerous tissues. Next, the putative functions of triplet SSR-containing genes were analyzed. In cancerous tissue, EST-SSRs produce different types of proteins. Chromodomain helicase DNA binding proteins were one of the major protein products of EST-SSRs in the cancerous library, while these proteins were not produced from EST-SSRs in normal tissue. For the first time, the findings of this study confirmed that EST-SSRs in normal lung tissues are different than in unhealthy tissues, and tagged ESTs with SSRs cause remarkable differences in amino acid and protein expression patterns in cancerous tissue. We suggest that EST-SSRs and EST-SSRs differentially expressed in cancerous tissue may be suitable candidate markers for lung cancer diagnosis and prediction.
串联重复序列存在于高等生物的编码和非编码序列中。这些序列可用于癌症遗传学和诊断,以揭示肿瘤形成和进展的遗传基础。在这项研究中,通过比较正常和肺癌组织中的 EST-SSR 进行了 EST-SSR 分布与肺癌之间可能存在的关系的研究。虽然肿瘤组织中的 EST-SSR 分布相似,但正常组织和肿瘤组织之间的分布不同。三核苷酸串联重复序列高度不同;肺癌 EST 中的三核苷酸数量是正常组织的 3 倍。正常组织和癌组织之间存在显著的负相关,表明癌组织产生不同类型的三核苷酸。在癌组织中,GGC 和 CGC 是表达频率较高的三核苷酸,但这些 SSR 在正常组织中不表达。与 EST 水平相似,正常组织和癌组织之间 EST-SSR 衍生氨基酸的表达模式也存在显著差异。Arg、Pro、Ser、Gly 和 Lys 是癌组织中最丰富的氨基酸,而 Leu、Cys、Phe 和 His 在正常组织中的含量明显高于癌组织。接下来,分析了含有三核苷酸 SSR 的基因的可能功能。在癌组织中,EST-SSR 产生不同类型的蛋白质。染色质解旋酶 DNA 结合蛋白是癌组织中 EST-SSR 的主要蛋白质产物之一,而这些蛋白质不是由正常组织中的 EST-SSR 产生的。本研究首次证实,正常肺组织中的 EST-SSR 与不健康组织中的 EST-SSR 不同,并且带有 SSR 的 EST 导致癌组织中氨基酸和蛋白质表达模式的显著差异。我们认为,EST-SSR 和癌组织中差异表达的 EST-SSR 可能是肺癌诊断和预测的合适候选标志物。