LncRNAfunc 2.0: an evidence-integrated knowledgebase for regulatory and functional interpretation of lncRNAs in cancer

Abstract

Long non-coding RNAs (lncRNAs) play diverse regulatory roles in cancer, yet their functional interpretation remains largely based on molecular associations and computational predictions, while experimentally derived evidence is fragmented across heterogeneous resources. Here, we present lncRNAfunc 2.0, an updated knowledgebase for systematic functional interpretation of cancer lncRNAs through multi-source evidence integration. Compared with the previous version, lncRNAfunc 2.0 reprocesses pan-cancer data from The Cancer Genome Atlas, incorporates normal-tissue and cancer-cell-line contexts from GTEx and CCLE, substantially expands binding and interaction evidence, and introduces perturbation evidence for lncRNAs and their regulators. These resources are integrated with association-based analyses and computational predictions as complementary evidence for interpreting lncRNA-associated regulatory relationships. lncRNAfunc 2.0 organizes functional knowledge into six biological dimensions: dysregulation, upstream regulation, lncRNA-mediated mRNA regulation, transcript remodeling, protein regulation, and tumor phenotypes. This framework connects regulatory determinants of lncRNAs with their downstream molecular relationships and phenotypic associations, including mRNA regulation, alternative splicing, protein regulation, survival, molecular and immune phenotypes, and drug response. Overall, lncRNAfunc 2.0 provides an evidence-integrated framework for exploring context-dependent lncRNA functions and regulatory mechanisms across cancers. lncRNAfunc 2.0 is freely available at https://lncrnafunc.xu-bioinfo.com/.