Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA.
Department of Otolaryngology-Head and Neck Surgery, UC San Diego School of Medicine, University of California, La Jolla, CA 92093, USA.
Int J Mol Sci. 2024 Oct 2;25(19):10631. doi: 10.3390/ijms251910631.
Transfer-RNA-derived fragments (tRFs) are a novel class of small non-coding RNAs that have been implicated in oncogenesis. tRFs may act as post-transcriptional regulators by recruiting AGO proteins and binding to highly complementary regions of mRNA at seed regions, resulting in the knockdown of the transcript. Therefore, tRFs may be critical to tumorigenesis and warrant investigation as potential biomarkers. Meanwhile, the incidence of papillary thyroid carcinoma (PTC) has increased in recent decades and current diagnostic technology stands to benefit from new detection methods. Although small non-coding RNAs have been studied for their role in oncogenesis, there is currently no standard for their use as PTC biomarkers, and tRFs are especially underexplored. Accordingly, we aim to identify dysregulated tRFs in PTC that may serve as biomarker candidates. We identified dysregulated tRFs and driver genes between PTC primary tumor samples (n = 511) and adjacent normal tissue samples (n = 59). Expression data were obtained from MINTbase v2.0 and The Cancer Genome Atlas. Dysregulated tRFs and genes were analyzed in tandem to find pairs with anticorrelated expression. Significantly anticorrelated tRF-gene pairs were then tested for potential binding affinity using RNA22-if a heteroduplex can form via complementary binding, this would support the hypothesized RNA silencing mechanism. Four tRFs were significantly dysregulated in PTC tissue ( < 0.05), with only AsnGTT 3'-tRF being upregulated. Binding affinity analysis revealed that tRF-30-RY73W0K5KKOV (AsnGTT 3'-tRF) exhibits sufficient complementarity to potentially bind to and regulate transcripts of SLC26A4, SLC5A8, DIO2, and TPO, which were all found to be downregulated in PTC tissue. In the present study, we identified dysregulated tRFs in PTC and found that AsnGTT 3'-tRF is a potential post-transcriptional regulator and biomarker.
转移 RNA 衍生片段(tRFs)是一类新的小非编码 RNA,它们与肿瘤发生有关。tRFs 可能通过招募 AGO 蛋白并与 mRNA 的高度互补区域结合在种子区域,从而导致转录物的下调,从而作为转录后调节剂发挥作用。因此,tRFs 可能对肿瘤发生至关重要,并值得作为潜在的生物标志物进行研究。同时,近年来甲状腺乳头状癌(PTC)的发病率有所增加,当前的诊断技术需要新的检测方法。尽管小非编码 RNA 已被研究用于其在肿瘤发生中的作用,但目前尚无将其用作 PTC 生物标志物的标准,而 tRFs 的研究尤其不足。因此,我们旨在鉴定 PTC 中可能作为生物标志物候选物的失调 tRFs。我们鉴定了 PTC 原发肿瘤样本(n = 511)和相邻正常组织样本(n = 59)之间失调的 tRF 和驱动基因。表达数据来自 MINTbase v2.0 和 The Cancer Genome Atlas。对失调的 tRF 和基因进行了串联分析,以找到表达呈反相关的基因对。然后使用 RNA22 测试具有显著反相关的 tRF-基因对的潜在结合亲和力-如果互补结合可以形成异源双链体,则这将支持假设的 RNA 沉默机制。在 PTC 组织中,有 4 个 tRF 显著失调(<0.05),只有 AsnGTT 3'-tRF 上调。结合亲和力分析表明,tRF-30-RY73W0K5KKOV(AsnGTT 3'-tRF)与 SLC26A4、SLC5A8、DIO2 和 TPO 的转录本具有足够的互补性,这些转录本在 PTC 组织中均下调。在本研究中,我们鉴定了 PTC 中的失调 tRFs,并发现 AsnGTT 3'-tRF 是一种潜在的转录后调节剂和生物标志物。