Circular RNAs (circRNAs) have played an essential role in cancer development. This study aimed to illustrate the impact and potential mechanism of circRACGAP1 action in NSCLC development. The expression patterns of circRACGAP1, miR-1296, and CDK2 in NSCLC tissues and cell lines were analysed by RT-qPCR. The function of circRACGAP1 in NSCLC cell proliferation and apoptosis was investigated using the CCK-8 assay, flow cytometry, TUNEL staining, and Western blot. The interaction among circRACGAP1, miR-1296, and CDK2 was clarified by dual-luciferase reporter assay while the correlation was confirmed by the Pearson correlation coefficient. The expression of circRACGAP1 and CDK2 was up-regulated in NSCLC tissues, while the expression of miR-1296 was down-regulated. Cell function studies further revealed that circRACGAP1 could promote NSCLC cell proliferation, accelerate the cell cycle process, up-regulate B-cell lymphoma 2 (Bcl2) expression, and down-regulate Bcl2-associated X (Bax) expression. miR-1296 was identified as a downstream target to reverse circRACGAP1-mediated cell proliferation. miR-1296 directly targeted the 3'-UTR of CDK2 to regulate proliferation and apoptosis of NSCLC cells. Additionally, the dual-luciferase reporter assay and Pearson correlation coefficient analysis proved that circRACGAP1 acted in NSCLC cells by negatively regulating miR-1296 expression and positively regulating CDK2 expression. In summary, our study revealed that circRACGAP1 promoted NSCLC cell proliferation by regulating the miR-1296/CDK2 pathway, providing potential diagnostic and therapeutic targets for NSCLC.
- MeSH
- apoptóza * genetika MeSH
- cyklin-dependentní kinasa 2 * metabolismus genetika MeSH
- kruhová RNA * genetika metabolismus MeSH
- lidé MeSH
- mikro RNA * genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- nádory plic * genetika patologie metabolismus MeSH
- nemalobuněčný karcinom plic * genetika patologie metabolismus MeSH
- proliferace buněk * genetika MeSH
- proteiny aktivující GTPasu genetika metabolismus MeSH
- regulace genové exprese u nádorů MeSH
- signální transdukce genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Small extracellular vesicles (sEVs) secreted by various types of cells serve as crucial mediators of intercellular communication within the complex tumour microenvironment (TME). Tumour-derived small extracellular vesicles (TDEs) are massively produced and released by tumour cells, recapitulating the specificity of their cell of origin. TDEs encapsulate a variety of RNA species, especially messenger RNAs, microRNAs, long non-coding RNAs, and circular RNAs, which release to the TME plays multifaced roles in cancer progression through mediating cell proliferation, invasion, angiogenesis, and immune evasion. sEVs act as natural delivery vehicles of RNAs and can serve as useful targets for cancer therapy. This review article provides an overview of recent studies on TDEs and their RNA cargo, with emphasis on the role of these RNAs in carcinogenesis.
- MeSH
- extracelulární vezikuly * metabolismus MeSH
- kruhová RNA genetika metabolismus MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- mezibuněčná komunikace MeSH
- mikro RNA genetika metabolismus MeSH
- nádorové mikroprostředí * MeSH
- nádory * patologie genetika metabolismus MeSH
- RNA dlouhá nekódující genetika MeSH
- RNA genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Mutations in the splicing factor 3b subunit 1 (SF3B1) gene are frequent in myelodysplastic neoplasms (MDS). Because the splicing process is involved in the production of circular RNAs (circRNAs), we investigated the impact of SF3B1 mutations on circRNA processing. Using RNA sequencing, we measured circRNA expression in CD34+ bone marrow MDS cells. We defined circRNAs deregulated in a heterogeneous group of MDS patients and described increased circRNA formation in higher-risk MDS. We showed that the presence of SF3B1 mutations did not affect the global production of circRNAs; however, deregulation of specific circRNAs was observed. Particularly, we demonstrated that strong upregulation of circRNAs processed from the zinc finger E-box binding homeobox 1 (ZEB1) transcription factor; this upregulation was exclusive to SF3B1-mutated patients and was not observed in those with mutations in other splicing factors or other recurrently mutated genes, or with other clinical variables. Furthermore, we focused on the most upregulated ZEB1-circRNA, hsa_circ_0000228, and, by its knockdown, we demonstrated that its expression is related to mitochondrial activity. Using microRNA analyses, we proposed miR-1248 as a direct target of hsa_circ_0000228. To conclude, we demonstrated that mutated SF3B1 leads to deregulation of ZEB1-circRNAs, potentially contributing to the defects in mitochondrial metabolism observed in SF3B1-mutated MDS.
Circular RNAs (circRNA) have gained recent interest due to their functional versatility due to their interactions with other RNA species and proteins, all of which underline complex regulatory networks involved in pathogenic mechanisms. As a result, recent insights in circRNA biology are investigating their biomarker and therapeutic potential. One such circRNA is CircFOXO3, which consists of the circularized second exon of the FOXO3 mRNA, a member of the forkhead box transcription factor family involved in the regulation of developmental programs. Recent research focused on the role of circFOXO3 in the context of cancer has highlighted several implications in key tumorigenesis mechanisms, thus consolidating its relevance among other identified circRNAs. In this paper, we will focus on the currently identified case-specific implications of circFOXO3 in cancer, with a focus on the circFOXO3-miRNA-mRNA regulatory networks, its interactions with different proteins, and their cumulated biological effects upon tumor development. Therefore, we aim to provide an integrated perspective of the mechanistic implications of circFOXO3 in different cancers while also highlighting its biomarker or therapeutic potential based on the current evidence.
- MeSH
- genové regulační sítě * MeSH
- kruhová RNA genetika MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- mikro RNA genetika MeSH
- nádory genetika patologie MeSH
- regulace genové exprese u nádorů * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Circular RNAs (circRNAs) constitute a recently recognized group of noncoding transcripts that function as posttranscriptional regulators of gene expression at a new level. Recent developments in experimental methods together with rapidly evolving bioinformatics approaches have accelerated the exploration of circRNAs. The differentiation of hematopoietic stem cells into a broad spectrum of specialized blood lineages is a tightly regulated process that depends on a multitude of factors, including circRNAs. However, despite the growing number of circRNAs described to date, the roles of the majority of them in hematopoiesis remain unknown. Given their stability and disease-specific expression, circRNAs have been acknowledged as novel promising biomarkers and therapeutic targets. In this paper, the biogenesis, characteristics, and roles of circRNAs are reviewed with an emphasis on their currently recognized or presumed involvement in hematopoiesis, especially in acute myeloid leukemia and myelodysplastic syndrome.
- MeSH
- akutní myeloidní leukemie krev genetika MeSH
- hematopoéza * MeSH
- kruhová RNA krev genetika MeSH
- lidé MeSH
- myelodysplastické syndromy krev genetika MeSH
- nádorové biomarkery krev genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Lung cancer is one of the main causes of cancer-related death in the world, especially due to its frequency and ineffective therapeutically approaches in the late stages of the disease. Despite the recent advent of promising new targeted therapies, lung cancer diagnostic strategies still have difficulty in identifying the disease at an early stage. Therefore, the characterizations of more sensible and specific cancer biomarkers have become an important goal for clinicians. Circular RNAs (circRNAs), a type of RNA with covalently closed continuous loop structures that display high structural resistance and tissue specificity pointed toward a potential biomarker role. Current investigations have identified that circRNAs have a prominent function in the regulation of oncogenic pathways, by regulating gene expression both at transcriptional and post-transcriptional level. The aim of this review is to provide novel information regarding the implications of circRNAs in lung cancer, with an emphasis on the role in disease development and progression. Initially, we explored the potential utility of circRNAs as biomarkers, focusing on function, mechanisms, and correlation with disease progression in lung cancer. Further, we will describe the interaction between circRNAs and other non-coding species of RNA (particularly microRNA) and their biological significance in lung cancer. Describing the nature of these interactions and their therapeutic potential will provide additional insight regarding the altered molecular landscape of lung cancer and consolidate the potential clinical value of these circular transcripts. This article is categorized under: RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development.
- MeSH
- cílená molekulární terapie MeSH
- kruhová RNA chemie genetika MeSH
- lidé MeSH
- nádorové biomarkery * MeSH
- nádory plic farmakoterapie genetika metabolismus patologie MeSH
- regulace genové exprese u nádorů * MeSH
- RNA interference MeSH
- signální transdukce MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
