Comparative Analysis of Altered lncRNA and mRNA Expression Profiles in RMI1-Knockdown Cells Following Ionizing Radiation Exposure

Abstract

This study analyzes RNA sequencing data to explore the molecular functions of RecQ-mediated genome instability protein 1 (RMI1) in ionizing radiation (IR)-induced DNA damage, as its underlying mechanisms remain unclear. Long non-coding RNA (lncRNA) and messenger RNA (mRNA) expression profiles were examined in control (C0), RMI1 knockdown (B0), and their irradiated cells (C8 and B8). Differentially expressed lncRNAs (DE-lncRNAs) and mRNAs (DE-mRNAs) were identified and validated by RT-qPCR. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) pathway, and protein-protein interaction network (PPI) and pan-cancer analyses were conducted. The nuclear colocalization of RMI1 with γH2AX and PLK1 following IR was confirmed by immunofluorescence. 33 DE-lncRNAs and 133 DE-mRNAs (B0 vs. C0) were identified, while 44 DE-lncRNAs and 139 DE-mRNAs (B8 vs. C8) were found. Functional enrichment analyses associated these genes mainly with cell cycle-related kinase activity, RAS signaling pathway, and DNA damage response. PPI and pan-cancer analyses suggested that RMI1, PLK1, CDC20, and PARP10 as potential interacting partners in DNA repair. RMI1 and PLK1 colocalized in the nucleus and were associated with poor liver hepatocellular carcinoma prognosis. These findings provide new insights into the molecular mechanisms by which RMI1 regulates DNA repair following IR exposure.