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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1517459

Downregulation of hnRNPA1 inhibits Hepatocellular Carcinoma Cell progression by modulating alternative splicing of ZNF207 Exon 9

Provisionally accepted
Qi Ouyang Qi Ouyang 1,2Wenhui He Wenhui He 1Yiping Guo Yiping Guo 1Lin Li Lin Li 1Ying Mao Ying Mao 1Xiang Li Xiang Li 2Shuanglin Xiang Shuanglin Xiang 1Xiang Hu Xiang Hu 1*Jun He Jun He 2
  • 1 College of Life Sciences, Hunan Normal University, Changsha, China
  • 2 Changsha Hospital for Maternal and Child Health Care,Hunan Normal University, Chang Sha, China

The final, formatted version of the article will be published soon.

    Hepatocellular carcinoma (HCC) represents the most prevalent liver cancer and ranks among the top causes of cancer-related deaths globally. Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) plays a crucial role in RNA metabolism including RNA splicing, stability, and transport, as well as the processing of pre-mRNA into mature mRNA. This study highlighted the significant role of hnRNPA1 in the advancement of HCC, noting a marked upregulation of hnRNPA1 in HCC tissues, which correlated with decreased survival outcomes. Comparative analyses showed that hnRNPA1 expression was significantly higher in HCC tissues than in non-tumor tissues such as B16-F10, and U251. Deeper exploration using RNA-seq of hnRNPA1-knockdown cells revealed that hnRNPA1 altered critical pathways involved in tumorigenesis, apoptosis, and cell proliferation. Silencing hnRNPA1 in Hep G2 cells led to decreased cell proliferation and migration, along with increased expression of the pro-apoptotic protein Bax and activation of caspase-3. Significantly, our findings demonstrated that hnRNPA1 banded to ZNF207, and controlled the skipping of exon 9 in ZNF207, impacting cell proliferation and migration.This modulation of ZNF207 splicing by hnRNPA1 affected the PI3K/Akt/mTOR signaling pathway, which is essential for cell growth and survival. Collectively, our results emphasize the critical function of hnRNPA1 in the progression of HCC through its regulation of alternative splicing and its interactions with vital cellular pathways. These results not only deepen our knowledge of the molecular processes driving HCC but also underscore potential therapeutic targets within the hnRNPA1-ZNF207 interaction.

    Keywords: liver cancer, Zinc finger protein 207, Alternative splice, gene regulation, PI3K/AKT/mTOR

    Received: 26 Oct 2024; Accepted: 09 Dec 2024.

    Copyright: © 2024 Ouyang, He, Guo, Li, Mao, Li, Xiang, Hu and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Xiang Hu, College of Life Sciences, Hunan Normal University, Changsha, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.