Dysregulation of pseudouridylation in small RNAs contributes to papillary thyroid carcinoma metastasis.

IF 5.3 2区医学 Q1 ONCOLOGY Cancer Cell International Pub Date : 2024-10-14 DOI:10.1186/s12935-024-03482-3

Xi Wang, Hengyuan Gao, Wenjun Pu, Zhipeng Zeng, Nan Xu, Xunpeng Luo, Donge Tang, Yong Dai

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Abstract

Background: Previous studies have indicated that ψ-modified small RNAs play crucial roles in tumor metastasis. However, the ψ-modified small RNAs during metastasis of PTC are still unclear.

Methods: We compared the pseudouridine synthase 7 (PUS7) alteration between metastatic and non-metastatic PTCs, and investigated its correlation with clinicopathological features. Additionally, we employed a small RNA ψ modification microarray to examine the small RNA ψ modification profile in both metastatic and non-metastatic PTCs, as well as paired paracancerous tissues. The key molecule involved in ψ modification, pre-miR-8082, was identified and found to regulate the expression of CD47. Experiments in vitro were conducted to further investigate the function of PUS7 and CD47 in PTC.

Results: Our results demonstrated that PUS7 was down-regulated in PTC and was closely associated with metastasis. Moreover, the ψ modification of pre-miR-8082 was found to be decreased, resulting in down-expression of pre-miR-8082 and miR-8082, leading to the loss of the inhibitory effect on CD47, thereby promoting tumor migration.

Conclusions: Our study demonstrates that PUS7 promotes the inhibition of CD47 and inhibits metastasis of PTC cells by regulating the ψ modification of pre-miR-8082. These results suggest that PUS7 and ψ pre-miR-8082 may serve as potential targets and diagnostic markers for PTC metastasis.

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小核糖核酸假苷酸化失调导致甲状腺乳头状癌转移

背景：以往的研究表明，ψ修饰的小RNA在肿瘤转移中起着至关重要的作用。然而，PTC 转移过程中的ψ修饰小 RNA 仍不清楚：方法：我们比较了转移性和非转移性PTC的假尿苷合成酶7（PUS7）改变，并研究了其与临床病理特征的相关性。此外，我们还利用小 RNA ψ修饰芯片研究了转移性和非转移性 PTC 以及配对癌旁组织的小 RNA ψ修饰概况。研究发现了参与ψ修饰的关键分子pre-miR-8082，并发现它能调控CD47的表达。为了进一步研究 PUS7 和 CD47 在 PTC 中的功能，我们进行了体外实验：结果：我们的研究结果表明，PUS7在PTC中下调，并与转移密切相关。此外，研究还发现pre-miR-8082的ψ修饰减少，导致pre-miR-8082和miR-8082下调，从而失去对CD47的抑制作用，进而促进肿瘤迁移：我们的研究表明，PUS7通过调节pre-miR-8082的ψ修饰，促进对CD47的抑制并抑制PTC细胞的转移。这些结果表明，PUS7 和 ψ pre-miR-8082 可作为 PTC 转移的潜在靶点和诊断标志物。

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来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.