Recent studies indicate that long noncoding RNAs (lncRNAs) can act as competing endogenous RNAs (ceRNAs) to indirectly regulate mRNAs through shared microRNAs, which represents a novel layer of RNA crosstalk and plays critical roles in the development of tumor. However, the global regulation landscape and characterization of these lncRNA related ceRNA crosstalk in cancers is still largely unknown.
Here, researchers from Harbin Medical University systematically characterized the lncRNA related ceRNA interactions across 12 major cancers and the normal physiological states by integrating multidimensional molecule profiles of more than 5000 samples. This study suggest the large difference of ceRNA regulation between normal and tumor states and the higher similarity across similar tissue origin of tumors. The ceRNA related molecules have more conserved features in tumor networks and they play critical roles in both the normal and tumorigenesis processes. Besides, lncRNAs in the pan-cancer ceRNA network may be potential biomarkers of tumor. By exploring hub lncRNAs, the researchers found that these conserved key lncRNAs dominate variable tumor hallmark processes across pan-cancers. Network dynamic analysis highlights the critical roles of ceRNA regulation in tumorigenesis. By analyzing conserved ceRNA interactions, they found that miRNA mediate ceRNA regulation showed different patterns across pan-cancer; while analyzing the cancer specific ceRNA interactions reveal that lncRNAs synergistically regulated tumor driver genes of cancer hallmarks. Finally, they found that ceRNA modules have the potential to predict patient survival.
The properties of pan-cancer ceRNA molecules
A. Proportion of lncRNAs in pan-cancer ceRNA networks that involved in each lncRNA class. B. Proportion of PCGs in pan-cancer ceRNA networks that are tissue specific and essential genes. C. Chromosome distribution of lncRNA-mRNA ceRNA pairs across 12 cancers. Dark green (light green) represent percent of ceRNA pairs in which lncRNA and PCG located in different (same) chromosome in normal ceRNA networks. Dark red (light red) represent percent of ceRNA pairs in which lncRNA and PCG located in different (same) chromosome in tumor ceRNA networks. D. P-value of hypergeometric test that evaluated significance of lncRNAs, PCGs and miRNAs that mediated ceRNA interactions enriched in the corresponding cancer related molecule (lncRNA/miRNA/PCG) sets. E. Jaccard coefficient matrix for PCGs in pan-cancer ceRNA networks and cancer hallmark processes.
Overall, this study systematically dissected the lncRNA related ceRNA networks in pan-cancer that shed new light on understanding the molecular mechanism of tumorigenesis.