Ye Jiankui, Chen Yu, Shao Zhuowei, Wu Yili, Li You, Fang Shuai, Wu Shibo
Department of Respiratory Medicine, The Affiliated Lihuili Hospital of Ningbo University, Zhejiang, China.
Health Science Center, Ningbo University, Zhejiang, China.
J Cell Mol Med. 2024 Dec;28(24):e70291. doi: 10.1111/jcmm.70291.
Transfer RNA-derived fragments (tRFs) are a new class of small non-coding RNAs. Recent studies suggest that tRFs participate in some pathological processes. However, the biological activities and processes of tRFs in lung cancer cells remain mainly unclear. In the present investigation, we employed tRNA-derived small RNA (tsRNA) sequencing to predict differentially expressed tsRNAs in lung cancer cells, and nine tsRNAs with significant expression alterations were validated using qPCR. Wound healing, colony formation, transwell invasion and CCK-8 assays were performed to detect the effects of tRF-16 on cell function. Western blotting evaluated the relationship between tRF-16 and the IGF2BP1 axis. Our findings demonstrated that tRF-16 expression was substantially downregulated in lung cancer cells. TRF-16 could inhibit lung cancer cells' ability to increase, migrate, invade and obtain radiation resistance. Furthermore, tRF-16 decreases the stability of CPT1A by impairing the binding of IGF2BP1 to CPT1A. As a result, the fatty acid metabolism in lung cancer cells was inhibited. Finally, tRF-16 also inhibits lung cancer cell proliferation in vivo. This study shows that tRF-16 plays a crucial regulatory role in the proliferation of lung cancer cells and may represent a novel avenue for their regulation.
转运RNA衍生片段（tRFs）是一类新型的小非编码RNA。最近的研究表明，tRFs参与了一些病理过程。然而，tRFs在肺癌细胞中的生物学活性和过程仍主要不清楚。在本研究中，我们采用tRNA衍生的小RNA（tsRNA）测序来预测肺癌细胞中差异表达的tsRNAs，并使用qPCR验证了9个表达有显著变化的tsRNAs。进行伤口愈合、集落形成、Transwell侵袭和CCK-8测定以检测tRF-16对细胞功能的影响。蛋白质免疫印迹法评估了tRF-16与IGF2BP1轴之间的关系。我们的研究结果表明，tRF-16在肺癌细胞中的表达显著下调。TRF-16可以抑制肺癌细胞的增殖、迁移、侵袭能力并获得辐射抗性。此外，tRF-16通过损害IGF2BP1与CPT1A的结合来降低CPT1A的稳定性。结果，肺癌细胞中的脂肪酸代谢受到抑制。最后，tRF-16在体内也抑制肺癌细胞增殖。本研究表明，tRF-16在肺癌细胞增殖中起关键调节作用，可能代表了一种新的调控途径。
