LncRNA AP003469.2 promotes hepatocellular carcinoma progression by regulating cuproptosis via the miR-4732-3p/LIPT1 axis
- 1Department of Breast and Thyroid Surgery, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi) , , ,
- 2Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University , , ,
- 3Department of Oncology, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi) , , ,
Abstract
Background: Hepatocellular carcinoma (HCC) is a malignant tumor characterized by high recurrence and metastasis rates, as well as a poor prognosis. Cuproptosis is a form of programmed cell death driven by abnormal copper-ion metabolism. Existing studies have shown that its occurrence is closely regulated and associated with the progression of HCC. However, it is still unclear how long non-coding RNAs (lncRNAs) control the process in HCC. The purpose of this work is to clarify how the lncRNA AP003469.2 influences cuproptosis and promotes the development of HCC.
Methods: This study utilized RNA sequencing data from the TCGA-LIHC dataset to screen for cuproptosis-related lncRNAs exhibiting significant expression differences. Following the initial screening, the expression of lncRNA AP003469.2 was validated using qRT-PCR. Subsequent in vitro and in vivo studies confirmed AP003469.2’s biological role in HCC. To understand the fundamental mechanisms, we determined the subcellular localization of the proteins using nuclear–cytoplasmic fractionation and fluorescence in situ hybridization (FISH). The regulatory relationships between miR-4732-3p and LIPT1 and between AP003469.2 and miR-4732-3p were then verified using dual-luciferase reporter assays. In addition, we utilized Western blotting, copper assays, CCK-8, and immunohistochemistry to evaluate related proteins and markers indicative of cuproptosis.
Results: A poor prognosis was observed to be positively correlated with elevated expression of AP003469.2 in HCC. In both in vivo and in vitro experimental methods, AP003469.2 stimulated important malignant characteristics in HCC cells, including invasion, migration, and proliferation. Furthermore, by controlling LIPT1 expression and modulating copper homeostasis and important proteins, including FDX1, SLC31A1, and HSP70, AP003469.2 acts as a molecular sponge for miR-4732-3p, attenuating cuproptosis.
Conclusion: Our research demonstrated that the AP003469.2/miR-4732-3p/LIPT1 axis could suppress cuproptosis to promote HCC progression. Therefore, AP003469.2 may serve as a target for HCC treatment or diagnosis.
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BibTeX
@article{huo2026lncrna,
title = {{LncRNA AP003469.2 promotes hepatocellular carcinoma progression by regulating cuproptosis via the miR-4732-3p/LIPT1 axis}},
author = {Jinlong Huo and Shuman Kuang and Lin Wu and Dong Ou},
journal = {Frontiers in oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1874176},
url = {https://europepmc.org/article/PMC/PMC13669170},
note = {CC BY},
}
RIS
TY - JOUR
TI - LncRNA AP003469.2 promotes hepatocellular carcinoma progression by regulating cuproptosis via the miR-4732-3p/LIPT1 axis
AU - Jinlong Huo
AU - Shuman Kuang
AU - Lin Wu
AU - Dong Ou
PY - 2026
DA - 2026/10/01
JO - Frontiers in oncology
DO - 10.3389/fonc.2026.1874176
UR - https://europepmc.org/article/PMC/PMC13669170
AB - Background: Hepatocellular carcinoma (HCC) is a malignant tumor characterized by high recurrence and metastasis rates, as well as a poor prognosis. Cuproptosis is a form of programmed cell death driven by abnormal copper-ion metabolism. Existing studies have shown that its occurrence is closely regulated and associated with the progression of HCC. However, it is still unclear how long non-coding RNAs (lncRNAs) control the process in HCC. The purpose of this work is to clarify how the lncRNA AP003469.2 influences cuproptosis and promotes the development of HCC. Methods: This study utilized RNA sequencing data from the TCGA-LIHC dataset to screen for cuproptosis-related lncRNAs exhibiting significant expression differences. Following the initial screening, the expression of lncRNA AP003469.2 was validated using qRT-PCR. Subsequent in vitro and in vivo studies confirmed AP003469.2’s biological role in HCC. To understand the fundamental mechanisms, we determined the subcellular localization of the proteins using nuclear–cytoplasmic fractionation and fluorescence in situ hybridization (FISH). The regulatory relationships between miR-4732-3p and LIPT1 and between AP003469.2 and miR-4732-3p were then verified using dual-luciferase reporter assays. In addition, we utilized Western blotting, copper assays, CCK-8, and immunohistochemistry to evaluate related proteins and markers indicative of cuproptosis. Results: A poor prognosis was observed to be positively correlated with elevated expression of AP003469.2 in HCC. In both in vivo and in vitro experimental methods, AP003469.2 stimulated important malignant characteristics in HCC cells, including invasion, migration, and proliferation. Furthermore, by controlling LIPT1 expression and modulating copper homeostasis and important proteins, including FDX1, SLC31A1, and HSP70, AP003469.2 acts as a molecular sponge for miR-4732-3p, attenuating cuproptosis. Conclusion: Our research demonstrated that the AP003469.2/miR-4732-3p/LIPT1 axis could suppress cuproptosis to promote HCC progression. Therefore, AP003469.2 may serve as a target for HCC treatment or diagnosis.
SN - 2234-943X
ER -