CircUGP2 inhibits tumor progression via PI3K/AKT/mTOR signaling through sponging miR-137-3p and interacting with UPF1 in hepatocellular carcinoma
- 1Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University , ,
Abstract
Background: Circular RNA (circRNA) has been shown to have a pivotal role in the initiation and evolution of multiple tumors, but its function in hepatocellular carcinoma (HCC) requires further elucidation.
Methods: circUGP2 (hsa_circ_0001020) was identified in the GEO database by HCC circRNA microarray. Subsequently, an assessment was conducted to determine the biological effects of circUGP2, employing a series of analytical methods, including CCK8, EdU, colony formation, transwell, scratch assays, and in vivo experimentation. To explore the functions of circUGP2 as a sponge, including RNA pull-down, microRNA-seq, fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP), and luciferase reporter assays were employed. Mass spectrometry (MS), RIP, and co-inmunoprecipitation (Co-IP) were employed to examine the interaction between cirrcUGP2 and up-frameshift protein 1 (UPF1).
Results: circUGP2 was downregulated in HCC tissues and cells, which inhibited the growth and spread of HCC in vitro and in vivo . In the mechanisms, circUGP2 has the capacity to modulate KLF4 by sponging miR-137-3p, thereby suppressing HCC growth and migration. In addition, circUGP2 could combine with UPF1 and facilitate an interplay between UPF1 and AKT, influencing tumor progression in HCC via inactivation of the PI3K/AKT signaling pathway.
Conclusion: circUGP2 has a crucial function in HCC development by modulating the miR-137-3p/KLF4 axis to inactivate the PI3K/AKT/mTOR pathway and by interacting with UPF1. The findings indicate the potential of circUGP2 as a novel biomarker and target for HCC.
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BibTeX
@article{xie2026circugp2,
title = {{CircUGP2 inhibits tumor progression via PI3K/AKT/mTOR signaling through sponging miR-137-3p and interacting with UPF1 in hepatocellular carcinoma}},
author = {Longfei Xie and Suxin Li and Huahu Guo and Wenhui Zhang and Mengjie Shang and Bailin Cheng and Dingyang Li and Luhao Li and Zhaochen Liu and Lin Li and Liang Bao and Kaiwei Tian and Chengxuan Li and Xiaowei Dang},
journal = {Frontiers in immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1926747},
url = {https://europepmc.org/article/PMC/PMC13672610},
note = {CC BY},
}
RIS
TY - JOUR
TI - CircUGP2 inhibits tumor progression via PI3K/AKT/mTOR signaling through sponging miR-137-3p and interacting with UPF1 in hepatocellular carcinoma
AU - Longfei Xie
AU - Suxin Li
AU - Huahu Guo
AU - Wenhui Zhang
AU - Mengjie Shang
AU - Bailin Cheng
AU - Dingyang Li
AU - Luhao Li
AU - Zhaochen Liu
AU - Lin Li
AU - Liang Bao
AU - Kaiwei Tian
AU - Chengxuan Li
AU - Xiaowei Dang
PY - 2026
DA - 2026/10/02
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1926747
UR - https://europepmc.org/article/PMC/PMC13672610
AB - Background: Circular RNA (circRNA) has been shown to have a pivotal role in the initiation and evolution of multiple tumors, but its function in hepatocellular carcinoma (HCC) requires further elucidation. Methods: circUGP2 (hsa_circ_0001020) was identified in the GEO database by HCC circRNA microarray. Subsequently, an assessment was conducted to determine the biological effects of circUGP2, employing a series of analytical methods, including CCK8, EdU, colony formation, transwell, scratch assays, and in vivo experimentation. To explore the functions of circUGP2 as a sponge, including RNA pull-down, microRNA-seq, fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP), and luciferase reporter assays were employed. Mass spectrometry (MS), RIP, and co-inmunoprecipitation (Co-IP) were employed to examine the interaction between cirrcUGP2 and up-frameshift protein 1 (UPF1). Results: circUGP2 was downregulated in HCC tissues and cells, which inhibited the growth and spread of HCC in vitro and in vivo . In the mechanisms, circUGP2 has the capacity to modulate KLF4 by sponging miR-137-3p, thereby suppressing HCC growth and migration. In addition, circUGP2 could combine with UPF1 and facilitate an interplay between UPF1 and AKT, influencing tumor progression in HCC via inactivation of the PI3K/AKT signaling pathway. Conclusion: circUGP2 has a crucial function in HCC development by modulating the miR-137-3p/KLF4 axis to inactivate the PI3K/AKT/mTOR pathway and by interacting with UPF1. The findings indicate the potential of circUGP2 as a novel biomarker and target for HCC.
SN - 1664-3224
ER -