hnRNP Q/SYNCRIP interacts with LIN28B and modulates the LIN28B/let-7 axis in human hepatoma cells

Sep 22, 2026

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The RNA-binding protein LIN28B suppresses let-7 biogenesis, while the LIN28B/let-7 axis governs cell differentiation and is linked to multiple cancers. This study examines whether hnRNP Q (Q/SYNCRIP) regulates this axis. hnRNP Q was shown to interact with LIN28B in an RNA-dependent manner, and hnRNP Q knockdown reduced TRIM71 and LIN28B levels, increased let-7 family miRNAs, and lowered TRIM71 3'UTR let-7 reporter activity. Depletion of hnRNP Q inhibited proliferation of Huh7 cells and matched TCGA survival analyses, supporting hnRNP Q as a poor-prognosis marker in hepatocellular carcinoma.

LanguageEnglish

CategoryResearch & Report

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Pages20

Reading Time50 min

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Abstract

Introduction

PLOS ONE OPEN ACCESS Citation: Chang JJ-S, Lin T, Jhang X-Y, Chan S-P (2024) hnRNP Q/SYNCRIP interacts with LIN28Band modulates the LIN28B/let-7 axis in human hepatoma cells. PLoS ONE 19(7): e0304947 . [https://doi.org/10.1371/journal.pone.0304947](https://doi.org/10.1371/journal.pone.0304947) [Editor:](Editor: Massimo Caputi)[ Massimo Caputi](Editor: Massimo Caputi), Florida Atlantic University, UNITED STATES Received: December 1, 2023 Accepted: May 21, 2024 Published: July 8, 2024 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: [https://doi.org/10.1371/journal.pone.0304947](https://doi.org/10.1371/journal.pone.0304947) [Copyright:](Copyright:) © [2024 Chang](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. Data Availability Statement: All relevant data has been uploaded to the OSF repository and can be accessed at this link: [https://doi.org/10.17605/OSF](https://doi.org/10.17605/OSF). IO/JR2U8 . RESEARCH ARTICLE hnRNP Q/SYNCRIP interacts with LIN28B and modulates the LIN28B/let-7 axis in human hepatoma cells Jason Jei-Sheng Chang1,2☯, Ti Lin1☯, Xin-Yue Jhang1, Shih-Peng Chan1,3 * 1 Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan, 2 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, 3 Genome and Systems Biology Degree Program, College of Life Science, National Taiwan University, Taipei, Taiwan ☯ These authors contributed equally to this work. * [shihpengchan@ntu.edu.tw](shihpengchan@ntu.edu.tw) Abstract The RNA-binding protein LIN28B represses the biogenesis of the tumor suppressor let-7. The LIN28B/let-7axis 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-7axis in hepatocellular carcinoma. Introduction Post-transcriptional regulation is extensively modulated by RNA-binding proteins (RBPs) . Previous screens have identified over 1,500 RBPs that account for ~7 .5% of all protein-coding genes in humans [ 1] . RBPs interact with different types of RNAs, including mRNAs, miRNAs, snRNAs, snoRNAs, and lncRNAs, and regulate their processing, function, alternative splicing, polyadenylation, localization, stability, and translation [2] . Most RBPs contain at least one RNA-binding domain (RBD), a cat

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What effects did hnRNP Q knockdown have on let-7-related targets and cell behavior?

hnRNP Q knockdown reduced TRIM71 and LIN28B expression, increased let-7 family miRNA levels, reduced luciferase reporter activity linked to let-7 sites, and inhibited proliferation of Huh7 hepatoma cells. It also aligned with TCGA patient survival patterns indicating high hnRNP Q predicts poor outcome.

Sep 22, 2026

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