LncRNA AP003469.2 promotes hepatocellular carcinoma progression by regulating cuproptosis via the miR-4732-3p/LIPT1 axis.

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.