Work

Long non-coding RNA TRHDE-AS1 regulates SPRED1 in the MAPK/ERK signaling pathway to play a tumor-suppressive role in melanoma

Year: 2026

Type: article

Abstract: Background Melanoma, a highly aggressive skin cancer, is characterized by its poor prognosis and high mortality rate. Identifying novel biomarkers is crucial for enhancing its diagnosis and treatment. Long non-coding RNAs (lncRNAs), such as thyrotropin-releasing hormone degrading enzyme antisense RNA1 (TRHDE-AS1), have shown potential tumor-suppressive roles in various malignancies, although their function in melanoma remains poorly understood. This study investigates the effects of lncRNA TRHDE-AS1 on the biological behavior of A375 human malignant melanoma cells and explores its regulatory relationship with SPRED1, a known mediator of the MAPK/ERK signaling pathway. Methods We conducted loss- and gain-of-function experiments on A375 cells to assess the influence of lncRNA TRHDE-AS1 on cell viability, apoptosis, migration, and invasion. We utilized RT-qPCR, Western blotting, RNA pulldown assays, and in vivo xenograft models to investigate the underlying molecular mechanisms. Results Overexpression of lncRNA TRHDE-AS1 significantly reduced the viability of A375 cells compared to the control group, while silencing lncRNA TRHDE-AS1 led to an increase in cell viability. Flow cytometry revealed that lncRNA TRHDE-AS1 overexpression resulted in a significant increase in the apoptotic rate compared to controls. The Transwell invasion assay indicated that the number of invaded cells decreased with lncRNA TRHDE-AS1 overexpression, while lncRNA TRHDE-AS1 knockdown promoted invasion. Furthermore, Western blot and RT-qPCR analyses demonstrated that lncRNA TRHDE-AS1 overexpression elevated SPRED1 protein and mRNA levels while significantly decreasing the expression of p-ERK, RAS, and p-RAF proteins, suggesting a dampening effect on MAPK/ERK signaling. These effects on expression levels were abolished by lncRNA TRHDE-AS1 knockdown. In vivo experiments with xenograft models corroborated these findings, showing that tumors in the lncRNA TRHDE-AS1 overexpression group were notably smaller and weighed less than those in control groups after three weeks of observation. Conclusion LncRNA TRHDE-AS1 acts as a tumor suppressor in melanoma by enhancing the expression of SPRED1 and inhibiting the MAPK/ERK signaling pathway. These findings suggest that lncRNA TRHDE-AS1 could serve as a potential therapeutic target for melanoma treatment.

Source: Discover Oncology

DOI: 10.1007/s12672-026-05972-4