Transcription
regulatory networks perturbation contributes to the development
and progression of cancer, however, the discovery of the
determinants that mediated the transcriptional perturbations
remains a fundamental challenge for cancer biology.
Here, we proposed an integrated framework-LncMAP (LncRNA
Modulator Atlas in Pan-cancer), to systematic dissection of
lncRNA mediated transcriptional regulations perturbations in 20
types of cancer. We show that transcriptional perturbations
were widely mediated by lncRNAs via integration of genome wide
transcriptional regulations with paired lncRNA and gene
expression profiles. Analysis across a diverse set of human
cancers reveals three distinct types of lncRNA modulators, in
which pan-cancer modulators mediated more number of
transcriptional perturbations, expressed in multiple tissues,
were with higher conservation and enriched cancer related
variations. Strikingly, cancer with similar tissue origin share
lncRNA modulators which perturbed the regulations of cell cycle
and immune response related functions. Furthermore, we
identified a large number of lncRNA modulators with potential
biomedical significance, which show differentially expressed in
cancer or are strongly correlated with drug sensitivity across
cell lines. Further stratification of cancer patients based on
lncRNA mediated transcriptional perturbations identifies
subtypes with distinct survival rates. Finally, this
user-friendly platform was constructed for exploring the lncRNA
mediated transcriptional perturbations across cancer types.
Our study provides a systems-level dissection of lncRNA
mediated regulatory perturbations in cancer, also presented a
valuable tool and resource for investigating the function of
lncRNAs in cancer, greatly facilitating lncRNA-related
biological discoveries and therapeutic intervention. |
