Plasma tRNA-derived small RNAs signature as a predictive and prognostic biomarker in lung adenocarcinoma.
Plasma tRNA-derived small RNAs signature as a predictive and prognostic biomarker in lung adenocarcinoma.
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血浆tRNA衍生的小RNA标记作为肺腺癌的预测和预后生物标志物
DOI：
10.1186/s12935-022-02481-6
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发表时间：
2022-02-03
影响因子：
5.8
通讯作者：
Duan C
中科院分区：
文献类型：
--
作者：
Wang J;Liu X;Cui W;Xie Q;Peng W;Zhang H;Gao Y;Zhang C;Duan C
肺腺癌（LUAD）的发病率不断增加，因此，用于其早期诊断的新生物标志物变得比以往任何时候都更加重要。tRNA衍生的小RNA（transRNA-derived small RNA，tsRNA）是一类新的非编码RNA，在肿瘤生物学中具有重要的调控作用。这项研究旨在鉴定新的预测和预后的tsRNA生物标志物。从10个血浆样本（6个LUAD和4个正常，SRP 266333）和96个组织样本（48个LUAD和48个正常，SRP 133217）中鉴定并进行差异表达分析。然后构建了一个tsRNA-mRNA调控网络，寻找枢纽tsRNA。进行功能富集分析以推断与tsRNA相关的潜在途径。然后，使用支持向量机（SVM）算法来探索用于诊断LUAD的潜在生物标志物。最后，在A549和H1299细胞系中探索tRF-21-RK 9 P4 P9 L0的功能。LUAD患者与正常人的血浆和组织中的read分布有显著性差异。建立了由155个差异表达tsRNA（DEtsRNA）和406个差异表达mRNA（DEmRNA）组成的tsRNA-mRNA调控网络。三个tsRNA（tRF-16-L 85 J3 KE、tRF-21-RK 9 P4 P9 L0和tRF-16-PSQP 4PE）被鉴定为度> 100的枢纽基因。我们发现Co-DEmRNA（DEtsRNA靶mRNA和LUAD中差异表达mRNA的交叉）参与许多癌症途径。三个hub tsRNA表达诊断LUAD的AUC达到0.92。此外，在37对正常和LUAD组织中的三个枢纽tsRNA的qPCR验证与RNA-Seq结果一致。此外，tRF-21-RK 9 P4 P9 L0与LUAD预后呈负相关。抑制tRF-21-RK 9 P4 P9 L0表达可降低A549和H1299细胞的增殖、迁移和侵袭能力。这些发现将有助于我们进一步了解LUAD的分子机制，并有助于发现新的诊断生物标志物和治疗靶点。在线版本包含补充材料，可通过10.1186/s12935-022-02481-6获得。
The prevalence of lung adenocarcinoma (LUAD) has increased, thus novel biomarkers for its early diagnosis is becoming more important than ever. tRNA-derived small RNA (tsRNA) is a new class of non-coding RNA which has important regulatory roles in cancer biology. This study was designed to identify novel predictive and prognostic tsRNA biomarkers. tsRNAs were identified and performed differential expression analysis from 10 plasma samples (6 LUAD and 4 normal, SRP266333) and 96 tissue samples (48 LUAD and 48 normal, SRP133217). Then a tsRNA-mRNA regulatory network was constructed to find hub tsRNAs. Functional enrichment analysis was performed to infer the potential pathways associated with tsRNAs. Afterwards, a Support Vector Machine (SVM) algorithm was used to explore the potential biomarkers for diagnosing LUAD. Lastly, the function of tRF-21-RK9P4P9L0 was explored in A549 and H1299 cell lines. A significant difference of read distribution was observed between normal people and LUAD patients whether in plasma or tissue. A tsRNA-mRNA regulatory network consisting of 155 DEtsRNAs (differential expression tsRNAs) and 406 DEmRNAs (differential expression mRNAs) was established. Three tsRNAs (tRF-16-L85J3KE, tRF-21-RK9P4P9L0 and tRF-16-PSQP4PE) were identified as hub genes with degree > 100. We found Co-DEmRNAs (intersection of DEtsRNAs target mRNAs and differentially expressed mRNAs in LUAD) were engaged in a number of cancer pathways. The AUC of the three hub tsRNAs’ expression for diagnosing LUAD reached 0.92. Furthermore, the qPCR validation of the three hub tsRNAs in 37 paired normal and LUAD tissues was consistent with the RNA-Seq results. In addition, tRF-21-RK9P4P9L0 was negatively associated with LUAD prognosis. Inhibition of tRF-21-RK9P4P9L0 expression reduced the proliferation, migration and invasion ability of A549 and H1299 cell lines. These findings will help us further understand the molecular mechanisms of LUAD and contribute to novel diagnostic biomarkers and therapeutic target discovery. The online version contains supplementary material available at 10.1186/s12935-022-02481-6.
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