LncMAP: Pan-cancer atlas of long noncoding RNA-mediated transcriptional network perturbations

Abstract

Gene regulatory network perturbations contribute to the development and progression of cancer, however, molecular determinants that mediate transcriptional perturbations remain a fundamental challenge for cancer biology. We show that transcriptional perturbations are widely mediated by long noncoding RNAs (lncRNAs) via integration of genome-wide transcriptional regulation with paired lncRNA and gene expression profiles. Systematic construction of an LncRNA Modulator Atlas in Pan-cancer (LncMAP) reveals distinct types of lncRNA regulatory molecules, which are expressed in multiple tissues, exhibit higher conservation. Strikingly, cancers with similar tissue origin share lncRNA modulators which perturb the regulation of cell cycle and immune response-related functions. Furthermore, we identified a large number of pan-cancer lncRNA modulators with potential clinical significance, which are 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, we made a user-friendly web interface available for exploring lncRNA-mediated transcriptional perturbations across cancer types. Our study provides a systems-level dissection of lncRNA-mediated regulatory perturbations in cancer, and also presents a valuable tool and resource for investigating the function of lncRNAs in cancer.

MIR22HG acts as a tumor suppressor via TGFβ/SMAD signaling and facilitates immunotherapy in colorectal cancer

“…With the development of next-generation sequencing technology, it is realized that the most part of human genome is transcribed to noncoding RNAs [2]. Of these newly discovered RNA regulatory elements, long noncoding RNAs (lncRNAs) have been demonstrated to play critical roles in diverse cellular processes [3][4][5]. LncRNAs can serve as signal mediators, scaffold or molecular decoys to function in epigenetic, transcriptional and posttranscriptional regulation.…”

Expression of long non‐coding RNA ENSG00000226738 (LncKLHDC7B) is enriched in the immunomodulatory triple‐negative breast cancer subtype and its alteration promotes cell migration, invasion, and resistance to cell death

“…Previous studies and our results shown above indicated that lncRNA is differentially expressed between TN breast cancer subtypes, thus lncRNA may be explored as a new class of clinical biomarkers for therapy response or targets for drug discovery (Arun et al ., ; Prabhakar et al ., ; Wu and Du, ). To identify drug‐related lncRNA in breast cancer, we explored the association of the LncKLHDC7B levels and drug activity with the lncMAP tool (Li et al ., ) (http://bio-bigdata.hrbmu.edu.cn/LncMAP/index.jsp), which computes the Spearman correlation coefficient between lncRNA expression and the half maximal inhibitory concentration (IC 50 ) values of 24 drugs approved for oncology purposes in TNBC cell lines. We observed a significant negative correlation between the expression of LncKLHDC7B and concentrations of lapatinib and paclitaxel (Fig.…”

Pan-cancer characterization of immune-related lncRNAs identifies potential oncogenic biomarkers

“…Having demonstrated that ImmLnc can effectively identify immune-related lncRNAs, we next explored the application of ImmLnc for prioritizing cancer-related lncRNAs. Although an increasing number of lncRNAs have been identified by experimental and computational methods 3,37 , the identification of novel cancer lncRNAs based on large-scale experiments is expensive and time consuming. We hypothesized that if the lncRNA-pathway relationships can be observed in more cancer types, they are more likely to be involved in cancer.…”