Non-coding RNAs in cancers with chromosomal rearrangements: the signatures, causes, functions and implications

Abstract

Chromosomal translocation leads to the juxtaposition of two otherwise separate DNA loci, which could result in gene fusion. These rearrangements at the DNA level are catastrophic events and often have causal roles in tumorigenesis. The oncogenic DNA messages are transferred to RNA molecules, which are in most cases translated into cancerous fusion proteins. Gene expression programs and signaling pathways are altered in these cytogenetically abnormal contexts. Notably, non-coding RNAs have attracted increasing attention and are believed to be tightly associated with chromosome-rearranged cancers. These RNAs not only function as modulators in downstream pathways but also directly affect chromosomal translocation or the associated products. This review summarizes recent research advances on the relationship between non-coding RNAs and chromosomal translocations and on diverse functions of non-coding RNAs in cancers with chromosomal rearrangements.

The pleiotropic roles of circular and long noncoding RNAs in cutaneous melanoma

“…Interestingly, circRNAs or lncRNAs might also originate from chromosomal DNA translocations. However, the expression patterns and functions of these ncRNAs in solid tumors are still unclear [summarized in [38]].…”

Disease-Causing Mutations and Rearrangements in Long Non-coding RNA Gene Loci

“…Other lncRNAs, demarcating chromosomal translocation break points exist (Delihas, 2018) and remain to be mechanistically dissected or causally implicated in human diseases. Furthermore, altered activity of signaling pathways and transcription factors due to translocations affecting coding genes impacts the expression of disease-associated classical GENCODE lncRNAs and enhancer RNAs, thereby e.g., contributing to leukemia and drug-resistance (Teppo et al, 2016;Han et al, 2019;Ng et al, 2019). Additionally, lncRNAs may fuse to coding genes to promote their activation.…”

Fusion Genes and RNAs in Cancer Development

“…The abnormally small resulting chromosome, named the Philadelphia chromosome, was found in over 95% of patients with chronic myelogenous leukemia (CML) and consisted of the breakpoint cluster region ( BCR ) gene fused to the second exon of the Abelson murine leukemia viral oncogene homolog 1 ( ABL1 ) gene [ 8 , 9 ]. Additional examples of cancer-associated chromosomal aberrations have been identified in other hematological malignancies and sarcomas; for example, mixed lineage leukemia (MLL) fusions, RUNX1–RUNX1T1 and PML – RARα , EWSR1 – FLI1 and EVT6 – NTRK3 [ 10 , 11 ]. Although originally discovered in hematological malignancies, gene fusions are now known to occur in several solid tumor types [ 7 , 12 , 13 ].…”

“…LncRNAs also function in chromatin and genomic structural remodeling, RNA trafficking, RNA stabilization, transcriptional regulation, translation, signal pathway, and protein degradation [ 27 , 28 , 29 , 30 , 31 ]. Expression of lncRNA, miRNA, and snoRNA have shown close correlations with specific chromosomal rearrangements in cancers [ 10 , 32 , 33 , 34 ]. Moreover, fusion circRNAs (f-circRNAs) that are generated by chromosome rearrangement contribute to oncogenic roles [ 35 ].…”