Unveiling the oncogenic role of lncRNA PIG13-DT in hepatocellular carcinoma progression.

IF 4.6 4区 医学 Q2 ONCOLOGY
Cancer Biology & Therapy Pub Date : 2025-12-31 Epub Date: 2025-10-09 DOI:10.1080/15384047.2025.2567797
Hongjie Cai, Song Chen, Shuangyan Tang, Feng Shi, Dan Zeng, Zhiqiang Wu, Fan Wang, Shuqin Huang, Dongbing Li, Wenbo Guo
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引用次数: 0

Abstract

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality due to delayed diagnosis and poor prognosis. Long non-coding RNAs (lncRNAs) are key cancer regulators, yet the role of C1orf21-DT (PIG13-DT) in HCC remains unclear.

Methods: We evaluated PIG13-DT expression in HCC and paired adjacent non-tumorous tissues. Functional studies were conducted using cell culture, cell-derived xenotransplantation (CDX) models, and molecular techniques including RNA pull-down, mass spectrometry, RIP-qPCR, and RNA sequencing. We explored the interplay between PIG13-DT, RNA-binding protein YBX3, and USP15 mRNA.

Results: PIG13-DT was highly expressed in HCC tissues compared with normal tissues and associated with poor prognosis. Functionally, PIG13-DT enhanced cancer stem cell (CSC) function, reduced reactive oxygen species (ROS) levels, and promoted HCC cell proliferation and migration. Mechanistically, PIG13-DT interacted with YBX3, stabilizing YBX3 and promoting USP15 mRNA translation and stability, thus driving HCC progression. Clinical data from lenvatinib-treated HCC patients showed that PIG13-DT expression was correlated with poor treatment response.

Conclusion: Our study identifies a novel PIG13-DT/YBX3/USP15 axis driving HCC progression, suggesting PIG13-DT as a potential biomarker and therapeutic target. This work provides new insights into HCC molecular mechanisms and offers potential diagnostic and therapeutic implications.

揭示lncRNA PIG13-DT在肝细胞癌进展中的致癌作用
背景:肝细胞癌(HCC)是癌症相关死亡的主要原因,由于诊断延迟和预后不良。长链非编码rna (lncRNAs)是关键的癌症调节因子,但C1orf21-DT (PIG13-DT)在HCC中的作用尚不清楚。方法:我们评估了PIG13-DT在HCC和配对的邻近非肿瘤组织中的表达。功能研究采用细胞培养、细胞衍生异种移植(CDX)模型和分子技术,包括RNA下拉、质谱、RIP-qPCR和RNA测序。我们探索了PIG13-DT、rna结合蛋白YBX3和USP15 mRNA之间的相互作用。结果:与正常组织相比,PIG13-DT在HCC组织中高表达,且与预后差相关。在功能上,PIG13-DT增强了癌症干细胞(CSC)功能,降低了活性氧(ROS)水平,促进了HCC细胞的增殖和迁移。在机制上,PIG13-DT与YBX3相互作用,稳定YBX3并促进USP15 mRNA的翻译和稳定性,从而推动HCC的进展。来自lenvatinib治疗的HCC患者的临床数据显示PIG13-DT表达与治疗反应差相关。结论:我们的研究发现了一个新的PIG13-DT/YBX3/USP15轴驱动HCC进展,表明PIG13-DT是一个潜在的生物标志物和治疗靶点。这项工作为HCC分子机制提供了新的见解,并提供了潜在的诊断和治疗意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cancer Biology & Therapy
Cancer Biology & Therapy 医学-肿瘤学
CiteScore
7.00
自引率
0.00%
发文量
60
审稿时长
2.3 months
期刊介绍: Cancer, the second leading cause of death, is a heterogenous group of over 100 diseases. Cancer is characterized by disordered and deregulated cellular and stromal proliferation accompanied by reduced cell death with the ability to survive under stresses of nutrient and growth factor deprivation, hypoxia, and loss of cell-to-cell contacts. At the molecular level, cancer is a genetic disease that develops due to the accumulation of mutations over time in somatic cells. The phenotype includes genomic instability and chromosomal aneuploidy that allows for acceleration of genetic change. Malignant transformation and tumor progression of any cell requires immortalization, loss of checkpoint control, deregulation of growth, and survival. A tremendous amount has been learned about the numerous cellular and molecular genetic changes and the host-tumor interactions that accompany tumor development and progression. It is the goal of the field of Molecular Oncology to use this knowledge to understand cancer pathogenesis and drug action, as well as to develop more effective diagnostic and therapeutic strategies for cancer. This includes preventative strategies as well as approaches to treat metastases. With the availability of the human genome sequence and genomic and proteomic approaches, a wealth of tools and resources are generating even more information. The challenge will be to make biological sense out of the information, to develop appropriate models and hypotheses and to translate information for the clinicians and the benefit of their patients. Cancer Biology & Therapy aims to publish original research on the molecular basis of cancer, including articles with translational relevance to diagnosis or therapy. We will include timely reviews covering the broad scope of the journal. The journal will also publish op-ed pieces and meeting reports of interest. The goal is to foster communication and rapid exchange of information through timely publication of important results using traditional as well as electronic formats. The journal and the outstanding Editorial Board will strive to maintain the highest standards for excellence in all activities to generate a valuable resource.
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