Long non-coding RNA MIAT functions as a ceRNA to protect uveal melanoma from oxidative stress by sponging miR-4306...

Uveal melanoma (UVM) is a highly aggressive intraocular malignancy with limited treatment options and a poor prognosis, particularly following metastasis. Oxidative stress plays a complex, dual role in tumor progression, but the regulatory roles of long non-coding RNAs (lncRNAs) in the oxidative stress response within UVM remain largely unexplored. The objective of this study was to investigate the regulatory mechanism of the lncRNA MIAT/miR-4306/CXCR4 axis in modulating oxidative stress and apoptosis in uveal melanoma (UVM), and to develop an oxidative stress-related prognostic gene signature.

This study integrated transcriptomic data from UVM patient tissues and public databases to construct an oxidative stress-related competing endogenous RNA (ceRNA) network. Bioinformatic analyses, including differential expression, weighted gene co-expression network analysis, and prognostic modeling, were employed. The functional roles of the identified lncRNA MIAT, miR-4306, and CXCR4 in apoptosis and oxidative stress were investigated in UVM cell lines. Techniques included quantitative real time polymerase chain reaction (qRT-PCR), Western blot, flow cytometry for apoptosis, and assays for oxidative stress markers.

We identified a novel ceRNA axis wherein the lncRNA MIAT is upregulated in UVM and acts as a molecular sponge for miR-4306, leading to the derepression of its target gene, CXCR4. Functionally, lncRNA MIAT overexpression alleviated hydrogen peroxide (H₂O₂)-induced oxidative stress and apoptosis, while miR-4306 exerted opposing, tumor-suppressive effects. CXCR4 was confirmed as a direct target of miR-4306 and mediated the protective effects of the MIAT/miR-4306 axis on cell survival. Furthermore, a prognostic risk model based on oxidative stress-related genes from the network effectively stratified patients into high- and low-risk groups with distinct survival outcomes and immune infiltration patterns.

Our findings elucidated a critical lncRNA MIAT/miR-4306/CXCR4 regulatory axis that modulated oxidative stress resistance and apoptosis in UVM. This axis represented a promising therapeutic target, and the developed oxidative stress-related gene signature may serve as a valuable prognostic tool for UVM patients.