Wang Jun, Liu Xianyu, Cui Weifang, Xie Qun, Peng Wei, Zhang Heng, Gao Yang, Zhang Chunfang, Duan Chaojun
Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China.
Hunan Engineering Research Center for Pulmonary Nodules Precise Diagnosis & Treatment, Changsha, 410008, Hunan, People's Republic of China.
Cancer Cell Int. 2022 Feb 3;22(1):59. doi: 10.1186/s12935-022-02481-6.
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.
肺腺癌（LUAD）的患病率有所上升，因此用于其早期诊断的新型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（tsRNA）是一类新的非编码RNA，在癌症生物学中具有重要的调节作用。本研究旨在鉴定新型的预测性和预后性tsRNA生物标志物。
从10份血浆样本（6例LUAD和4例正常，SRP266333）和96份组织样本（48例LUAD和48例正常，SRP133217）中鉴定tsRNA并进行差异表达分析。然后构建tsRNA-mRNA调控网络以找到关键tsRNA。进行功能富集分析以推断与tsRNA相关的潜在途径。之后，使用支持向量机（SVM）算法探索用于诊断LUAD的潜在生物标志物。最后，在A549和H1299细胞系中探索tRF-21-RK9P4P9L0的功能。
无论是在血浆还是组织中，正常人和LUAD患者之间均观察到读数分布的显著差异。建立了一个由155个差异表达tsRNA（DEtsRNAs）和406个差异表达mRNA（DEmRNAs）组成的tsRNA-mRNA调控网络。鉴定出三个tsRNA（tRF-16-L85J3KE、tRF-21-RK9P4P9L0和tRF-16-PSQP4PE）为度数>100的关键基因。我们发现共差异表达mRNA（DEtsRNAs靶mRNA与LUAD中差异表达mRNA的交集）参与了许多癌症途径。这三个关键tsRNA表达用于诊断LUAD的AUC达到0.92。此外，在37对正常和LUAD组织中对这三个关键tsRNA进行的qPCR验证与RNA测序结果一致。此外，tRF-21-RK9P4P9L0与LUAD预后呈负相关。抑制tRF-21-RK9P4P9L0的表达降低了A549和H1299细胞系的增殖、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。
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