Identifying Differentially Expressed tRNA-Derived Small Fragments as a Biomarker for the Progression and Metastasis of Colorectal Cancer.
Identifying Differentially Expressed tRNA-Derived Small Fragments as a Biomarker for the Progression and Metastasis of Colorectal Cancer.
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DOI：
10.1155/2022/2646173
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Chen H;Xu Z;Cai H;Peng Y;Yang L;Wang Z
上皮-间质转化（epithelial-to-mesenchymal transition， EMT）是结直肠癌侵袭转移的关键步骤之一。到目前为止，EMT在CRC中的潜在机制仍不明确。因此，有必要更好地了解其致癌作用。转移rna衍生的小片段（tsRNAs）是一类新的小非编码rna (sncRNAs)，包括trna衍生的应激诱导rna （tiRNAs）和trna衍生的片段（tRFs），已被观察到在许多癌症中发挥重要作用。然而，CRC中trf与EMT之间的关系尚不清楚。在此，我们旨在研究trf在EMT中的参与及其对CRC发展的贡献。我们利用高通量测序和实时定量逆转录聚合酶链反应（qRT-PCR）技术，鉴定了TGF-β处理的结直肠癌HT29细胞与对照细胞中tsRNAs的差异表达。采用QRT-PCR验证68例CRC肿瘤样本（22例女性和46例男性）和邻近非肿瘤样本中的差异表达片段。分析tRFs表达与结直肠癌转移及临床分期的关系。同时分析tRF表达与总生存期（OS）的相关性。利用TargetScan和miRanda等多种生物信息学方法预测tsRNAs可能的靶基因，分析trf可能的功能。与对照细胞相比，TGF-β处理的HT29细胞中发现了一系列差异表达的tsRNAs。与邻近的非肿瘤组织相比，在结直肠癌组织中发现tRF-phe-GAA-031和tRF-VAL-TCA-002显著上调。与远处转移及临床分期有显著相关性。我们比较了肿瘤样本和非肿瘤组织在ROC曲线上的差异。trf - ph - gaa -031的ROC曲线下面积（AUC）高达0.7554(95%置信区间：0.6739 ~ 0.8369,p < 0.0001)， tRF-VAL-TCA-002的AUC高达0.7313（95%置信区间：0.6474 ~ 0.8151,p < 0.0001）。在OS分析中，较高的tRF-phe-GAA-031和tRF-VAL-TCA-002表达与CRC患者较短的生存期相关。在结直肠癌的EMT过程中发现了一系列差异表达的tsrna。而tRF-phe-GAA-031和tRF-VAL-TCA-002在结直肠癌组织中表达较高，可能在结直肠癌转移中发挥重要作用。同时，它们可能是临床治疗结直肠癌的潜在生物标志物和干预靶点。
The epithelial-to-mesenchymal transition (EMT) is one key step for the invasion and metastasis of colorectal cancer (CRC). Up until now, the underlying mechanism of EMT in CRC is still unpromising. Thus, it is essential to have a better understanding of its carcinogenesis. The transfer RNA-derived small fragments (tsRNAs) are a new group of small noncoding RNAs (sncRNAs), including tRNA-derived stress-induced RNAs (tiRNAs) and tRNA-derived fragments (tRFs), which have been observed to play an important role in many cancers. However, the relationship between tRFs and EMT in CRC is still unknown. Herein, we aimed to investigate the involvement of tRFs in EMT and its contribution to CRC development. We identified the differentially expressed tsRNAs in colorectal cancer cell line HT29 treated with TGF-β compared with control cells by using high-throughput sequencing and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). QRT-PCR was conducted to validate the differentially expressed fragments in 68 CRC tumor samples (22 women and 46 men) and adjacent nontumor samples. The association of the expression of tRFs with CRC metastasis and clinical stage was analyzed. Meanwhile, the correlation between tRF expression and overall survival (OS) was also analyzed. TargetScan and miRanda and multiple bioinformatic approaches were used to predict the possible target genes of tsRNAs and analyze possible functions of the tRFs. A series of differentially expressed tsRNAs were identified in TGF-β-treated HT29 cells compared with control cells. tRF-phe-GAA-031 and tRF-VAL-TCA-002 were found to be significantly upregulated in CRC tissues compared to adjacent nontumor tissues. They were significantly correlated with distant metastasis and clinical stage. We compared the differences between tumor samples and nontumor tissues from the ROC curves. The area under the ROC curve (AUC) was up to 0.7554 (95% confidence interval: 0.6739 to 0.8369, p < 0.0001) for tRF-Phe-GAA-031 and up to 0.7313 (95% confidence interval: 0.6474 to 0.8151, p < 0.0001) for tRF-VAL-TCA-002. For OS analysis, higher tRF-phe-GAA-031 and tRF-VAL-TCA-002 expressions were associated with shorter survival for CRC patients. A series of differentially expressed tsRNAs are identified in the EMT process of CRC. And tRF-phe-GAA-031 and tRF-VAL-TCA-002 are higher expressed in CRC tissues, and they might play an important role in the metastasis of CRC. Meanwhile, they may be potential biomarkers and intervention targets in the clinical treatment of CRC.
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