CircPIK3C3 inhibits hepatocellular carcinoma progression and lenvatinib resistance by suppressing the Wnt/β-catenin pathway via the miR-452-5p/SOX15 axis.

IF 3.4 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics Pub Date : 2025-01-23 DOI:10.1016/j.ygeno.2025.110999

Feng Yuan, Yongchang Tang, Hao Liang, Mingbo Cao, Yupeng Ren, Yuxuan Li, Gaoyuan Yang, Zhaozhong Zhong, Zhiyong Xiong, Zhiwei He, Meihai Deng, Zhicheng Yao

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引用次数: 0

Abstract

Introduction: Resistance to lenvatinib limits the effectiveness of the targeted treatments for HCC. However, the exact mechanism behind this resistance remains elusive. Current research suggests that circular RNA (circRNA) is pivotal in mediating drug resistance during targeted treatments.

Objectives: To investigate the influence of circRNA on HCC progression and its resistance to lenvatinib.

Methods: We identified the crucial circRNA hsa_circ_0005711 (circPIK3C3) through bioinformatics. Study (in-vitro and in-vivo) on the expression of circPIK3C3 (measured by qRT-PCR) and its association with progress of HCC patients including lenvatinib resistance were performed. Techniques such as dual-luciferase reporter assays, RNA FISH, RAP, and AGO2-RIP were employed for discerning circPIK3C3's specific mechanisms related to progression of HCC and its lenvatinib resistance.

Results: Study (in-vitro and in-vivo) revealed that circPIK3C3 exhibited reduced expression and lenvatinib resistance in HCC, which was intimately tied to patient outcomes. Moreover, circPIK3C3 elevated SOX15 expression while suppressing the signaling pathway related to Wnt/β-catenin via inhibition of miR-452-5p through a competitive endogenous RNA (ceRNA) network. This, in turn, mitigated HCC progression and its resistance to lenvatinib.

Conclusion: CircPIK3C3 is instrumental in the disease progression and resistance to Lenvatinib in HCC. It presents a potential therapeutic avenue for patients with lenvatinib-resistant HCC and could serve as a valuable molecular marker for forecasting lenvatinib resistance in HCC patients.

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来源期刊

Genomics 生物-生物工程与应用微生物

CiteScore

9.60

自引率

2.30%

发文量

260

审稿时长

60 days

期刊介绍： Genomics is a forum for describing the development of genome-scale technologies and their application to all areas of biological investigation. As a journal that has evolved with the field that carries its name, Genomics focuses on the development and application of cutting-edge methods, addressing fundamental questions with potential interest to a wide audience. Our aim is to publish the highest quality research and to provide authors with rapid, fair and accurate review and publication of manuscripts falling within our scope.