A new type of RNAs was identified from genes traditionally thought to express messenger or linear ncRNA (noncoding RNA) only. They were subsequently named as circRNAs (circular RNAs) due to the covalently closed structure. Accumulating studies were performed to explore the expression profile of circRNAs in different cell types and diseases, the outcomes totally changed our view of ncRNAs, which was thought to be junk by-products in the process of gene transcription, and enriched our poor understanding of its underlying functions. The expression profile of circRNAs is tissue-specific and alters across various stages of cell differentiation. The biological function of circRNAs is multi-faceted, involving five main features (sponge effect, post-transcriptional regulation, rolling circle translation, circRNA-derived pseudogenes and splicing interference) and varying differently from the locations, binding sites and acting modes of circRNAs. The regulating role of circRNAs is not isolated but through an enormous complicated network involving mRNAs, miRNAs and proteins. Although most of the potential functions still remain unclear, circRNAs have been proved to be ubiquitous and critical in regulating cellular processes and diseases, especially in cancers, from the laboratory to the clinic. Herein, we review circRNAs’ classification, biogenesis and metabolism, their well-studied and anticipated functions, the current understanding of the potential implications of circRNAs in tumorigenesis and cancer targeted therapy.

Numerous studies confirmed that aberrant miRNAs expression contributes to multiple myeloma (MM) development and progression. However, the roles of specific miRNAs in MM remain to be investigated. In present study, we demonstrated that miR-410 expression was increased in MM newly diagnosed and relapsed tissues and cell lines. Clinical analysis revealed that miR-410 was positively correlated with advanced ISS stage. Moreover, high miR-410 expression in MM patients showed an obvious shorter overall survival and progression-free survival. Gain- and loss-of function experiments indicated that miR-410 promoted cell proliferation, cell cycle progression and apoptosis inhibition both in vitro and in vivo. Moreover, KLF10 was identified as a direct downstream target of miR-410 in MM cells, and mediated the functional influence of miR-410 in MM, resulting in PTEN/AKT activation. In clinical samples of MM, miR-410 inversely correlated with KLF10. Alteration of KLF10 expression or AKT inhibitor at least partially abolished the biological effects of miR-410 on MM cells. Furthermore, downregulated expression of lncRNA OIP5-AS1 was inversely correlated with miR-410 expression in MM tissues. LncRNA OIP5-AS1 could modulate the miR-410 expression and regulate its target KLF10/PTEN/AKT-mediated cellular behaviors. Taken together, this research supports the first evidence that lncRNA OIP5-AS1 loss-induced miR-410 accumulation facilitates cell proliferation, cycle progression and apoptosis inhibition by targeting KLF10 via activating PTEN/PI3K/AKT pathway in MM.

Highlights d Loss of METTL3 inhibits proliferation and differentiation of hematopoietic stem cells d Depletion of m 6 A results in aberrant dsRNA formation of long m 6 A-modified transcripts d Loss of METTL3 induces deleterious innate immune responses in hematopoiesis d Mavs and Rnasel depletion partially rescue defects in Vav-Cre + -Mettl3 fl/

Background/Aims: Circular RNAs (circRNAs) are a family of novel non-coding RNAs associated with various diseases, especially cancer. Recent studies have demonstrated that circRNAs participate in pathogenesis mainly by acting as microRNA (miRNA) sponges. The expression profile of circRNAs in acute myeloid leukemia (AML) has rarely been reported. Methods: Profiles of circRNAs were analyzed using an Arraystar human circRNA microarray with 5 bone marrow samples from patients with newly diagnosed AML and 5 from patients with iron-deficiency anemia. Quantitative reverse transcription PCR was used to validate the expression pattern of circRNAs. Furthermore, circRNA–miRNA network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were applied. Results: CircRNA microarray analysis revealed that 698 circRNAs were differentially expressed in AML patients, with 282 circRNAs found to be upregulated and 416 to be downregulated. Quantitative reverse transcription PCR showed that circ-ANAPC7 was significantly upregulated in AML. Bioinformatics analysis predicted that circ-ANAPC7 acts as a sponge for the miR-181 family, KEGG analysis revealed that it is associated with cancer-related pathways, and GO analysis indicated that most of its target genes are involved in biological processes. Conclusions: These findings show that circ-ANAPC7 is a promising biomarker for AML, and that it might participate in AML pathogenesis by acting as a sponge for the miR-181 family.