From circRNAs to fusion circRNAs in hematological malignancies

Abstract

Circular RNAs (circRNAs) represent a type of endogenous noncoding RNA generated by back-splicing events. Unlike the majority of RNAs, circRNAs are covalently closed, without a 5 ′ end or a 3 ′ poly(A) tail. A few circRNAs can be associated with polysomes, suggesting a protein-coding potential. CircRNAs are not degraded by RNA exonucleases or ribonuclease R and are enriched in exosomes. Recent developments in experimental methods coupled with evolving bioinformatic approaches have accelerated functional investigation of circRNAs, which exhibit a stable structure, a long half-life, and tumor specificity and can be extracted from body fluids and used as potential biological markers for tumors. Moreover, circRNAs may regulate the occurrence and development of cancers and contribute to drug resistance through a variety of molecular mechanisms. Despite the identification of a growing number of circRNAs, their effects in hematological cancers remain largely unknown. Recent studies indicate that circRNAs could also originate from fusion genes (fusion circRNAs, f-circRNAs) next to chromosomal translocations, which are considered the primary cause of various cancers, notably hematological malignancies. This Review will focus on circRNAs and f-circRNAs in hematological cancers.

Validating Cell Surface Proteases as Drug Targets for Cancer Therapy: What Do We Know, and Where Do We Go?

“…MMP9 + DPP4 + exosomes derived from glioma are potent inducers of angiogenesis ex vivo through the phenotypic modulation of endothelial cells [261]. In addition, exosomes carry genetic materials, including DNA, mRNA, miRNA, long noncoding (lnc) RNA, and circular (cir) RNA [262,263]. Deregulated miRNA, lncRNA, and cirRNA enhance mRNA expression in human cancers [262,263].…”

“…In addition, exosomes carry genetic materials, including DNA, mRNA, miRNA, long noncoding (lnc) RNA, and circular (cir) RNA [262,263]. Deregulated miRNA, lncRNA, and cirRNA enhance mRNA expression in human cancers [262,263]. Exosomal miRNAs (miR-100-5p and miR-21-5p) derived from prostate CSCs increase MMP2/9 expression and enhance the MMP-mediated migration of tumour cells, contributing to local invasion and premetastatic niche formation [264].…”

Exosomal circSTRBP from cancer cells accelerates gastric cancer progression via regulating miR-1294/miR-593-3p/E2F2 axis

“…circRNAs are enriched in cancer cell-derived exosomes. [16,17] These extracellular vesicles play pivotal roles in cellular communication; a variety of cargo, including DNA, RNA, proteins, and lipids, carried by exosomes can be taken up by other cells, thereby impacting the functional properties of recipient cells. [16] In cancer, exosomes were shown to make an important contribution to creating a favorable microenvironment for disease progression and metastases.…”

Clinical Implications of Circulating Circular RNAs in Lung Cancer

“…Although the exact mechanism through which circRNAs are generated has not been elucidated yet, circRNAs are considered to be generated with the help of specialized factors during the splicing process. An alternative "back-splicing" that joins together the 5 GU donor site at the downstream intron and the 3 AG acceptor site at the upstream exon promotes RNA circularization [20]. circRNAs can form from all precursor RNA regions including exons (protein-coding or untranslated regions) and introns.…”