Construction and analysis of lncRNA-lncRNA synergistic networks to reveal clinically relevant lncRNAs in cancer

Abstract

Long non-coding RNAs (lncRNAs) play key roles in diverse biological processes. Moreover, the development and progression of cancer often involves the combined actions of several lncRNAs. Here we propose a multi-step method for constructing lncRNA-lncRNA functional synergistic networks (LFSNs) through co-regulation of functional modules having three features: common coexpressed genes of lncRNA pairs, enrichment in the same functional category and close proximity within protein interaction networks. Applied to three cancers, we constructed cancer-specific LFSNs and found that they exhibit a scale free and modular architecture. In addition, cancer-associated lncRNAs tend to be hubs and are enriched within modules. Although there is little synergistic pairing of lncRNAs across cancers, lncRNA pairs involved in the same cancer hallmarks by regulating same or different biological processes. Finally, we identify prognostic biomarkers within cancer lncRNA expression datasets using modules derived from LFSNs. In summary, this proof-of-principle study indicates synergistic lncRNA pairs can be identified through integrative analysis of genome-wide expression data sets and functional information.

LINC00467 promotes cell proliferation and metastasis by binding with IGF2BP3 to enhance the mRNA stability of TRAF5 in hepatocellular carcinoma

“…Recently, accumulating studies have revealed the lncRNA‐lncRNA synergistic networks in many diseases . For example, lncRNA UCA1 and MAPK1 can synergistically affect cell proliferation and migration in lung cancer .…”

LncRNA FAL1 is a negative prognostic biomarker and exhibits pro‐oncogenic function in osteosarcoma

“…It is well‐known that the circulating lncRNA can be detected in patients with cancer. LncRNA can serve as a diagnostic marker in patients due to its effects on cancer progression . FAL1 is a recently identified 566nt‐long lncRNA located at 1q21.2, which is implicated in the development of many types of tumors, particularly ovarian cancer .…”

Downregulation of long noncoding RNA LOC101928134 inhibits the synovial hyperplasia and cartilage destruction of osteoarthritis rats through the activation of the Janus kinase/signal transducers and activators of transcription signaling pathway by upregulating IFNA1

“…LncRNA plays important roles in the proliferation, apoptosis, and invasiveness of tumor cells, and engages in the metastatic capacity of cancers (Cai, Song, Cai, & Zhang, ). A recent study suggested that lncRNAs are differentially expressed in many human diseases, such as cancer, metabolic disease, cardiovascular disease, neurodegenerative disease, and psychiatric disease (Fu et al, ; Y. Li et al, ). LncRNA was upregulated in OA cartilage compared with normal samples and could induce degradation of cartilage extracellular matrix in vitro (Fu et al, ).…”