Comprehensive characterization of lncRNA-mRNA related ceRNA network across 12 major cancers

Abstract

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, we 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. Our 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, we 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, we 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, we found that ceRNA modules have the potential to predict patient survival. Overall, our study systematically dissected the lncRNA related ceRNA networks in pan-cancer that shed new light on understanding the molecular mechanism of tumorigenesis.

Long noncoding RNA RHPN1-AS1 promotes colorectal cancer progression via targeting miR-7-5p/OGT axis

“…Mounting evidence has demonstrated that lncRNAs are closely associated with normal physiological progresses and pathological change [26]. The aberrantly expressed lncRNAs could be applied as prediction biomarkers for many diseases, including cancers [27][28][29].…”

Roles and expression profiles of long non‐coding RNAs in triple‐negative breast cancers

“…An increasing number of researches have demonstrated the dysregulated expressions of lncRNAs in varieties of cancers, including breast cancer, cervical cancer, prostate cancer, oesophageal squamous cell carcinoma, colorectal cancer, nasopharyngeal carcinoma, hepatocellular carcinoma, osteosarcoma and gastric cancer [13]. One of the commonest dysregulation forms of lncRNA is elucidated by Iyer et al's [14]integrative analyses of approximately 7200 RNA-sequencing libraries from cancer and non-cancer tissues and cells, which identified over 8000 cancerrelated lncRNAs.…”

Identification of lncRNA–miRNA–mRNA regulatory network associated with Primary Open Angle Glaucoma

“…Hub nodes, which have been examined in some studies and are characterized by their high degree of connectivity to other nodes in the ceRNA network, can be used as topological properties of the ceRNA network to assess the significance of genes [39,40]. In the present study, four lncRNAs (DNAJC27-AS1, AF121898, OIP5-AS1, and SNX29P2) were observed to be topological hub nodes whose betweenness, network degree, and closeness centrality were significantly higher in comparison with other lncRNAs.…”