Inhibiting Melanoma Tumor Growth: The Role of Oxidative Stress-Associated LINC02132 and COPDA1 Long Non-Coding RNAs

jingwen Xu ¹ mingzhu Jin ¹ zhenzhen Mu ¹ zhengxiu Li ² Rui-qun Qi ² xiuping Han ¹ hanghang Jiang ^1*

• ¹ Department of Dermatology, Shengjing Hospital, China Medical University, Shenyang, China
• ² Department of Dermatology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China

Cutaneous melanoma is a type of malignant tumor that is challenging to predict and is readily stimulated by various factors. Oxidative stress can induce damage and alterations in melanocytes, subsequently triggering a series of immune responses. Given that oxidative stress is a prevalent tumor stimulus, we aimed to enhance melanoma prediction by identifying lncRNA signatures associated with oxidative stress. In our research, we screened for oxidative stressrelated lncRNAs that could improve melanoma patient prognosis using the TCGA and GTEx databases. A total of 472 samples from the TCGA-SKCM dataset, including 17,622 genes, were analyzed. Utilizing differentially expressed oxidative stress-related lncRNAs (DE-OSlncRNAs), we constructed a Lasso regression model. Univariate Cox regression analysis was first performed to identify significant lncRNAs with P<0.05. Lasso regression was then used to select candidate lncRNAs, and a Cox regression model was built to predict risk values. Thirteen lncRNAs were identified as significant prognostic factors. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves were employed to validate the effectiveness of our model. The results aligned with clinical findings, reinforcing the model's clinical relevance. Subsequently, we conducted immune infiltration analysis, immune checkpoint differential analysis, IC50 pharmaceutical analysis, and gene set enrichment analysis. All thirteen genes exhibited significant differential expression. Among these, we selected genes that were feasible for experimental validation, with a particular focus on LINC02132 and COPDA1. Four oxidative stress-related lncRNAs (COPDA1, LINC02132, LINC02812, and MIR205HG) were further validated by fluorescence in situ hybridization (FISH), with results consistent with our data analysis. The impact of LINC02132 and COPDA1 on melanoma prognosis was evaluated through qRT-PCR, Edu assay, wound healing assay, transwell assay, flow cytometry, and detection of ROS. Our findings suggest that targeting DE-OSlncRNAs or utilizing antioxidant drugs may enhance the prognosis of melanoma patients.