TRP Channel-related LncRNAs, AC092535.4 and LINC01637, As Novel Prognostic Biomarkers for Uveal Melanoma

Overview

Journal Front Genet

Date 2024 Aug 7

PMID 39109337

Authors

Min Zhang

Jinglan Ni

Dongyue Liu

Yubo Cui

Xiaochen Ma

Jun Zhao

Affiliations

Soon will be listed here.

Abstract

Introduction: Transient receptor potential (TRP) channels function as cellular sensors with a broad impact, and their dysregulation is linked to numerous cancers. The influence of TRP channel-related long noncoding RNAs (TCRLs) on uveal melanoma (UM) remains poorly understood.

Methods: We employed bioinformatics to examine the RNA-seq data and relevant clinical information of UM in the TCGA databases. By implementing coexpression analysis, we identified differentially expressed TCRLs. Using univariate Cox regression analysis, selection operator (LASSO) algorithm and stepwise regression, five key prognostic biomarkers were chosen. The high- and low-risk groups were divided based on the risk scores. Afterwards, the prediction performance of the signature was evaluated by receiver operating characteristic (ROC) curve and Kaplan-Meier (K-M) survival analysis. The functional enrichment analysis of TCRLs was also investigated. Following that, we examined immune cell infiltration, immune checkpoint expression, and tumor immune microenvironment between patients in high and low risk groups. TCRLs were validated using Random forests and multifactor Cox analysis. Candidate biomarkers were identified and screened. Finally, the effects of the candidate biomarkers on the proliferation, migration and invasion of UM cells were detected by CCK-8 assay, migration assay and perforation invasion assay.

Results: The risk score generated by five TCRLs demonstrated robust predictive power. The high-risk group exhibited a poorer prognosis, increased immune cell infiltration, and an active tumor immune microenvironment compared to the low-risk group. Furthermore, two TCRLs of risk score, AC092535.4 and LINC01637, were screened to multiplex modelling. The experiments demonstrated that UM cells were suppressed following AC092535.4 or LINC01637 knockdown.

Discussion: Two TCRLs, AC092535.4 and LINC01637, serve as novel prognostic biomarkers for uveal melanoma and may present potential therapeutic targets.

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