Dose-specific lncRNA-mRNA networks modulate DNA damage and immune responses in CD4⁺ T cells under simulated space UVC...

Ultraviolet-C (UVC) irradiation is a prevalent component of the extraterrestrial radiation spectrum. To explore how long non-coding RNAs (lncRNAs) orchestrate cellular responses under simulated space UVC radiation, we exposed human CD4⁺ T cells to varying doses of UVC (100-800 J/m²). High-dose (400 and 800 J /m²) exposure significantly reduced cell viability and elevated reactive oxygen species (ROS) levels, whereas low-dose (100 and 200 J/m²) exposure triggered only modest ROS increases without compromising cell survival. At 24 h post-irradiation, microarray profiling revealed that the low-dose group was found to have a total of 155 mRNAs and 62 lncRNAs with altered expression, which were enriched in DNA damage response and p53 signaling pathways. In contrast, the high-dose group exhibited 913 mRNAs and 913 lncRNAs linked to immune and metabolic pathways. Co-expression analyses identified distinct lncRNA-mRNA networks in response to different UVC doses. Specifically, three lncRNAs were found to be positively or negatively correlated with eight DNA-repair transcripts in the low-dose group, while four lncRNAs showed positive correlations with six immune-related mRNAs in the high-dose group. These expression changes were confirmed by RT-qPCR. Notably, survival analyses in melanoma datasets implicated CDKN1A, MDM2 and lncRNA CMAHP as potential prognostic targets. Collectively, our findings demonstrate that space-level UVC doses are interpreted by dose-specific lncRNA-mRNA networks that direct either DNA damage response or immune-defense programs in CD4⁺ T cells.