Numerous studies have demonstrated that lncRNAs could compete with other RNAs to bind
miRNAs, as competing endogenous RNAs (ceRNAs), to regulate each other. On the other hand, ceRNAs were found to be recurrently dysregulated in
cancer status. However, limited studies considered the upstream epigenetic regulatory factors that disrupted the normal competing mechanism. In the present study, we constructed the
lncRNA-associated dysregulated
ceRNA networks across eight
cancer types. lncRNAs in the individual dysregulated network and pan-
cancer core dysregulated
ceRNA subnetwork were found to play more important roles than mRNAs. Integrating
lncRNA methylation profiles, we identified 49 epigenetically related (ER) lncRNAs involved in the dysregulated
ceRNA networks, including 18 epigenetically activated (EA) lncRNAs, 18 epigenetically silenced (ES) lncRNAs, and 13 rewired ER lncRNAs across eight
cancer types. Furthermore, we evaluated the epigenetic regulating patterns of these lncRNAs and screened nine pan-
cancer ER lncRNAs (six EA and three ES lncRNAs). The nine lncRNAs were found to regulate the
cancer hallmarks by competing with mRNAs. Moreover, we found that integrating the expression and methylation profiles of the nine lncRNAs could predict
cancer incidence in eight
cancer types robustly and the
cancer outcome of several
cancer types. These results provide an improved understanding of methylation regulation to
ceRNA and offer novel potential molecular therapeutic targets for the diagnosis and prognosis across different
cancer types.