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Circular RNA profile indicates circular RNA VRK1 is negatively related with breast cancer stem cells.

ABSTRACT: Circular RNAs (circRNAs), a novel type of noncoding RNAs (ncRNAs), have been shown to be implicated in biological processes including cancer as gene expression regulators. However, the roles of circRNAs in cancer stem cells (CSCs) have been unexplored. In the present study, we screened the circRNA profile in breast cancer stem cells (BCSCs) using RNA-Sequencing. Here, 27 circRNAs were found to be aberrantly expressed. Of these, 19 circRNAs were downregulated and 8 were upregulated and some of these circRNAs were validated by Q-PCR. Furthermore, we constructed the circRNA/miRNA network by bioinformatics approaches and hypothesized that circRNAs might be involved in stemness of BCSCs via serving as miRNA sponges. Importantly, we found that circular RNA VRK1 (circVRK1) could suppress BCSC's expansion and self-renewal capacity. Collectively, the present work provides the first reported evidence of the circRNA profile and circRNA/miRNA interplay in BCSCs. In addition, these findings lay foundation to explore the functions of circRNAs in CSCs and indicate that circVRK1 might be a promising target for BCSCs.

SUBMITTER: Yan N

PROVIDER: S-EPMC5707054 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Circular RNA profile indicates circular RNA VRK1 is negatively related with breast cancer stem cells.

Yan Ningning N Xu Haiyan H Zhang Jinnan J Xu Liang L Zhang Yanyun Y Zhang Le L Xu Yingchun Y Zhang Fengchun F

Oncotarget 20170923 56

Circular RNAs (circRNAs), a novel type of noncoding RNAs (ncRNAs), have been shown to be implicated in biological processes including cancer as gene expression regulators. However, the roles of circRNAs in cancer stem cells (CSCs) have been unexplored. In the present study, we screened the circRNA profile in breast cancer stem cells (BCSCs) using RNA-Sequencing. Here, 27 circRNAs were found to be aberrantly expressed. Of these, 19 circRNAs were downregulated and 8 were upregulated and some of th ...[more]

PMID: 29221160

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Project description:BackgroundCervical cancer is one of the most common cancers in women worldwide. Malignant tumors develop resistance mechanisms and are less sensitive to or do not respond to irradiation. With the development of high-throughput sequencing technologies, circular RNA (circRNA) has been identified in an increasing number of diseases, especially cancers. It has been reported that circRNA can compete with microRNAs (miRNAs) to change the stability or translation of target RNAs, thus regulating gene expression at the transcriptional level. However, the role of circRNAs in cervical cancer and the radioresistance mechanisms of HeLa cells are unknown. The objective of this study is to investigate the role of circRNAs in radioresistance in HeLa cells.MethodsHigh-throughput sequencing and bioinformatics analysis of irradiated and sham-irradiated HeLa cells. The reliability of high-throughput RNA sequencing was validated using quantitative real-time polymerase chain reaction. The most significant circRNA functions and pathways were selected by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A circRNA-miRNA-target gene interaction network was used to find circRNAs associated with radioresistance. Moreover, a protein-protein interaction network was constructed to identify radioresistance-related hub proteins.ResultsHigh-throughput sequencing allowed the identification of 16,893 circRNAs involved in the response of HeLa cells to radiation. Compared with the control group, there were 153 differentially expressed circRNAs, of which 76 were up-regulated and 77 were down-regulated. GO covered three domains: biological process (BP), cellular component (CC) and molecular function (MF). The terms assigned to the BP domain were peptidyl-tyrosine dephosphorylation and regulation of cell migration. The identified CC terms were cell-cell adherens junction, nucleoplasm and cytosol, and the identified MF terms were protein binding and protein tyrosine phosphatase activity. The top five KEGG pathways were MAPK signaling pathway, endocytosis, axon guidance, neurotrophin signaling pathway, and SNARE interactions in vesicular transport. The protein-protein interaction analysis indicated that 19 proteins might be hub proteins.ConclusionsCircRNAs may play a major role in the response to radiation. These findings may improve our understanding of the role of circRNAs in radioresistance in HeLa cells and allow the development of novel therapeutic approaches.

Project description:As multicellular organisms age, they undergo a reduction in tissue and organ function. Researchers have put forward a theory that stem cell aging is the main factor responsible for decreased tissue and organ function. The adult stem cells guarantee the maintenance and repair of adult tissues and organs. Among adult stem cells, mesenchymal stem cells (MSCs) are emerging as hopeful candidates for cell-based therapy of numerous diseases. In recent years, high-throughput sequencing technologies have evolved to identify circular RNAs (circRNAs) associated with an increasing number of diseases, such as cancer and age-related diseases. It has been reported that circRNAs can compete with microRNAs (miRNAs) to affect the stability or translation of target RNAs and further regulate gene expression at the transcriptional level. However, the role of circRNAs expressed in MSCs in aging mechanisms has not yet been deciphered. The aim of this study was to explore and analyze the expression profiles of age-related circRNAs in MSCs. In this study, bone marrow MSCs were extracted from aged and young rats and analyzed using high-throughput sequencing and bioinformatics. The reliability of high-throughput RNA sequencing was verified by quantitative real-time polymerase chain reaction. The most important circRNA functions and pathways were further selected by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG) analysis. Age-related circRNAs were found in the circrNA-miRNA-mRNA interaction network. The results of high-throughput sequencing showed that 4,229 circRNAs were involved in age-related senescence of MSCs. Compared with the young group, there were 29 differentially expressed circRNAs in the aged group, of which four were upregulated and 25 were downregulated. GO analysis covered three domains: biological process (BP), cellular component (CC), and molecular function (MF). The terms assigned to the BP domain were cellular metabolic processes and cellular macromolecule metabolic processes. The identified CC terms were intracellular and intracellular part, and the identified MF terms were binding and protein binding. The top five KEGG pathways were mitophagy-animal-Rattus norvegicus, prostate cancer-Rattus norvegicus, pathways in cancer-Rattus norvegicus, lysosome-Rattus norvegicus, and autophagy-animal-Rattus norvegicus. Altogether, circRNAs may play a major role in age-related MSC senescence. This study provides new mechanistic insights into MSC senescence, possibly leading to novel therapeutic strategies for age-related diseases.

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Circular RNA profile indicates circular RNA VRK1 is negatively related with breast cancer stem cells.

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Circular RNA profile indicates circular RNA VRK1 is negatively related with breast cancer stem cells.

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