Integrated Transcriptomic and Network Analysis Identifies MILIP as a Central lncRNA Hub in the RNA-Binding Protein Regulatory Landscape of Colorectal Cancer

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide, characterized by complex molecular heterogeneity and dysregulated gene expression programs. Increasing evidence suggests that post-transcriptional regulation mediated by RNA-binding proteins (RBPs) and long non-coding RNAs (lncRNAs) plays a crucial role in tumor initiation and progression. However, the global regulatory architecture of RBP–lncRNA interactions in CRC remains incompletely understood. In this study, we integrated gene expression profiles of RBPs and lncRNAs to construct a comprehensive co-expression network based on Pearson correlation analysis. Significant RBP–lncRNA interactions were identified using thresholds of |r| > ۰.۵ and p < ۰.۰۵. The resulting regulatory network was visualized using a force-directed layout, and topological analysis was performed to identify hub genes based on node degree. Network analysis revealed a highly structured interaction landscape with distinct hub RBPs and lncRNAs, suggesting the presence of coordinated post-transcriptional regulatory modules in CRC. To validate network-derived findings, differential expression analysis was performed on five selected lncRNAs from TCGA datasets (EMSLR, MILIP, RIPK۲-DT, RNASEH۱-AS۱, and . Among these, MILIP was identified as the only overlapping gene between differentially expressed lncRNAs and network hub nodes. Further analysis of a MILIP-centered subnetwork demonstrated strong and multiple interactions between MILIP and RBPs, indicating its central position within the regulatory network. These findings suggest that MILIP may function as a key regulatory lncRNA in CRC, integrating both transcriptional dysregulation and network-level centrality. Overall, this integrative analysis provides new insights into the RBP–lncRNA regulatory landscape in CRC and highlights MILIP as a potential candidate for further functional investigation and biomarker development. These findings are hypothesis-generating and require experimental validation in future studies.

کلیدواژه ها:

Colorectal cancer ، RNA-binding proteins ، long non-coding RNAs ، gene co-expression network ، hub genes