RNA 结合蛋白 LIN28B 抑制肿瘤抑制因子 let-7 的生物发生。 LIN28B/let-7 轴调节细胞分化并与多种癌症相关。 RNA 结合蛋白 Q (hnRNP Q) 或 SYNCRIP（突触结合蛋白结合细胞质 RNA 相互作用蛋白）与癌症中的 mRNA 剪接、mRNA 转运、翻译和 miRNA 生物合成以及代谢有关。为了确定 hnRNP Q 是否在 LIN28B/let-7 轴中发挥作用，我们测试了 hnRNP Q 和 LIN28B 之间的相互作用。我们证明 hnRNP Q 以 RNA 依赖性方式与 LIN28B 相互作用。 hnRNP Q 的敲低会导致众所周知的 let-7 靶点 TRIM71（一种属于 RBCC/TRIM 家族的 E3 泛素连接酶）以及 LIN28B 的表达减少，LIN28B 的 mRNA 本身会被 let-7 下调。此外，hnRNP Q 敲低增加了 let-7 家族 miRNA 水平，并降低了与 TRIM71 3'UTR 或携带 8X let-7 互补位点的合成 3'UTR 融合的荧光素酶报告基因的活性。最后，hnRNP Q 的消耗抑制了肝细胞癌细胞系 Huh7 的增殖。这一观察结果与 TCGA 数据库中肝癌患者的生存曲线一致，这表明 hnRNP Q 的高表达是肝细胞癌个体预后不良的预后标志。总之，我们的研究结果表明 hnRNP Q 与 LIN28B 相互作用并调节肝细胞癌中的 LIN28B/let-7 轴。版权所有：© 2024 Chang 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

The RNA-binding protein LIN28B represses the biogenesis of the tumor suppressor let-7. The LIN28B/let-7 axis regulates cell differentiation and is associated with various cancers. The RNA-binding protein Q (hnRNP Q) or SYNCRIP (Synaptotagmin Binding Cytoplasmic RNA Interacting Protein) has been implicated in mRNA splicing, mRNA transport, translation, and miRNAs biogenesis as well as metabolism in cancer. To determine whether hnRNP Q plays a role in the LIN28B/let-7 axis, we tested for interactions between hnRNP Q and LIN28B. We demonstrated that hnRNP Q interacts with LIN28B in an RNA-dependent manner. Knockdown of hnRNP Q caused reduced expression of a well-known let-7 target TRIM71, an E3 ubiquitin ligase that belongs to the RBCC/TRIM family, and also LIN28B, whose mRNA itself is down-regulated by let-7. In addition, hnRNP Q knockdown increased let-7 family miRNA levels and reduced the activity of luciferase reporters fused with the TRIM71 3'UTR or a synthetic 3'UTR carrying 8X let-7 complementary sites. Finally, depletion of hnRNP Q inhibited the proliferation of a hepatocellular carcinoma cell line, Huh7. This observation is consistent with the survival curve for liver cancer patients from the TCGA database, which indicates that high expression of hnRNP Q is a prognostic marker for a poor outcome in individuals afflicted with hepatocellular carcinoma. Together, our findings suggest that hnRNP Q interacts with LIN28B and modulates the LIN28B/let-7 axis in hepatocellular carcinoma.Copyright: © 2024 Chang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.