Cancer LncRNA Census 2 (CLC2): an enhanced resource reveals clinical features of cancer lncRNAs

Abstract

Long non-coding RNAs (lncRNAs) play key roles in cancer and are at the vanguard of precision therapeutic development. These efforts depend on large and high-confidence collections of cancer lncRNAs. Here, we present the Cancer LncRNA Census 2 (CLC2). With 492 cancer lncRNAs, CLC2 is 4-fold greater in size than its predecessor, without compromising on strict criteria of confident functional/genetic roles and inclusion in the GENCODE annotation scheme. This increase was enabled by leveraging high-throughput transposon insertional mutagenesis screening data, yielding 92 novel cancer lncRNAs. CLC2 makes a valuable addition to existing collections: it is amongst the largest, contains numerous unique genes (not found in other databases) and carries functional labels (oncogene/tumour suppressor). Analysis of this dataset reveals that cancer lncRNAs are impacted by germline variants, somatic mutations and changes in expression consistent with inferred disease functions. Furthermore, we show how clinical/genomic features can be used to vet prospective gene sets from high-throughput sources. The combination of size and quality makes CLC2 a foundation for precision medicine, demonstrating cancer lncRNAs’ evolutionary and clinical significance.

LncRNAs in domesticated animals: from dog to livestock species

“…Note that these overlaps have been computed at the gene level given the uncertainty of isoform modelling with short-reads as explained in the main text first analysed in the context of dog breed phenotypic variations, such as the "drop ear" phenotype, in which case using GWAS one lncRNA was found to be closely associated to the MSRB3 gene involved in human deafness (Plassais et al 2019) (see below "GWAS hits involving lncRNAs"). Furthermore, given the combined interest for lncRNAs as potential cancer drivers/biomarkers (Huarte 2015;Vancura et al 2021) and dogs as natural and thus immunocompetent models for cancer analyses (Prouteau and André 2019), canine lncRNAs were analysed in three canine breeds (poodles, Labradors, and golden retrievers) predisposed to mucosal melanomas (MM). Using RNAseq in tumour and adjacent matched control tissues, more than 400 lncRNAs were shown to be differentially expressed between healthy and diseased animals, with 26 of these lncRNAs being reported to be conserved in humans (Hitte et al 2019).…”

Long non-coding RNAs: novel regulators of cellular physiology and function

“…Cancer is a highly complex disease whose hallmarks include, among others, immune evasion, genome instability, angiogenesis and sustained proliferation [ 23 , 24 ]. Databases such as Lnc2Cancer [ 19 ] and Cancer LncRNA Census [ 65 ] list lncRNAs already identified to be involved in cancer.…”

Urinary extracellular vesicles contain mature transcriptome enriched in circular and long noncoding RNAs with functional significance in prostate cancer

“…LncRNAs constitute the most prevalent family in human transcriptome and can exert a plethora of functions, such as epigenetic regulation, chromatin remodelling, regulation of proteins' activity and stability, mRNA stability and translation. They make an intimate part of mechanisms controlling cell/tissue homeostasis as well as various diseases including cancers (Rinn & Chang, 2012) now nicely reported in the CLC2 lncRNA database (Vancura et al, 2021). Although lncRNAs were initially defined as noncoding, several contain open reading frames (ORFs) that are translated into functional peptides and subjected to translation-dependent decay (Andjus et al, 2021;Chen, 2020).…”