scholarly journals Identification of Two Novel Circular RNAs Deriving from BCL2L12 and Investigation of Their Potential Value as a Molecular Signature in Colorectal Cancer

2020 ◽  
Vol 21 (22) ◽  
pp. 8867
Author(s):  
Paraskevi Karousi ◽  
Pinelopi I. Artemaki ◽  
Christina D. Sotiropoulou ◽  
Spyridon Christodoulou ◽  
Andreas Scorilas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Tnm Stage ◽  
Stage Ii ◽  
Molecular Signature ◽  
Circular Rnas ◽  
Tissue Samples ◽  
Related Family

The utility of circular RNAs (circRNAs) as molecular biomarkers has recently emerged. However, only a handful of them have already been studied in colorectal cancer (CRC). The purpose of this study was to identify new circRNAs deriving from BCL2L12, a member of the BCL2 apoptosis-related family, and investigate their potential as biomarkers in CRC. Total RNA extracts from CRC cell lines and tissue samples were reversely transcribed. By combining PCR with divergent primers and nested PCR followed by Sanger sequencing, we were able to discover two BCL2L12 circRNAs. Subsequently, bioinformatical tools were used to predict the interactions of these circRNAs with microRNAs (miRNAs) and RNA-binding proteins (RBPs). Following a PCR-based pre-amplification, real-time qPCR was carried out for the quantification of each circRNA in CRC samples and cell lines. Biostatistical analysis was used to assess their potential prognostic value in CRC. Both novel BCL2L12 circRNAs likely interact with particular miRNAs and RBPs. Interestingly, circ-BCL2L12-2 expression is inversely associated with TNM stage, while circ-BCL2L12-1 overexpression is associated with shorter overall survival in CRC, particularly among TNM stage II patients. Overall, we identified two novel BCL2L12 circRNAs, one of which can further stratify TNM stage II patients into two subgroups with substantially distinct prognosis.

scholarly journals Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Fei Long ◽  
Zhi Lin ◽  
Liang Li ◽  
Min Ma ◽  
Zhixing Lu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Circular Rnas ◽  
Future Perspectives ◽  
Cis Acting ◽  
New Class ◽  
Functional Peptides ◽  
Mirna Sponges

AbstractColorectal cancer (CRC) is a common hereditary tumor that is often fatal. Its pathogenesis involves multiple genes, including circular RNAs (circRNAs). Notably, circRNAs constitute a new class of noncoding RNAs (ncRNAs) with a covalently closed loop structure and have been characterized as stable, conserved molecules that are abundantly expressed in tissue/development-specific patterns in eukaryotes. Based on accumulating evidence, circRNAs are aberrantly expressed in CRC tissues, cells, exosomes, and blood from patients with CRC. Moreover, numerous circRNAs have been identified as either oncogenes or tumor suppressors that mediate tumorigenesis, metastasis and chemoradiation resistance in CRC. Although the regulatory mechanisms of circRNA biogenesis and functions remain fairly elusive, interesting results have been obtained in studies investigating CRC. In particular, the expression of circRNAs in CRC is comprehensively modulated by multiple factors, such as splicing factors, transcription factors, specific enzymes and cis-acting elements. More importantly, circRNAs exert pivotal effects on CRC through various mechanisms, including acting as miRNA sponges or decoys, interacting with RNA binding proteins, and even translating functional peptides. Finally, circRNAs may serve as promising diagnostic and prognostic biomarkers and potential therapeutic targets in the clinical practice of CRC. In this review, we discuss the dysregulation, functions and clinical significance of circRNAs in CRC and further discuss the molecular mechanisms by which circRNAs exert their functions and how their expression is regulated. Based on this review, we hope to reveal the functions of circRNAs in the initiation and progression of cancer and highlight the future perspectives on strategies targeting circRNAs in cancer research.

scholarly journals The effective function of circular RNA in colorectal cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mandana Ameli-Mojarad ◽  
Melika Ameli-Mojarad ◽  
Mahrooyeh Hadizadeh ◽  
Chris Young ◽  
Hosna Babini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Circular Rna ◽  
Circular Rnas ◽  
Colorectal Tumorigenesis ◽  
Non Coding Rnas ◽  
Mirna Sponges ◽  
Mechanisms Of Development

AbstractColorectal cancer (CRC) is the 3rd most common type of cancer worldwide. Late detection plays role in one-third of annual mortality due to CRC. Therefore, it is essential to find a precise and optimal diagnostic and prognostic biomarker for the identification and treatment of colorectal tumorigenesis. Covalently closed, circular RNAs (circRNAs) are a class of non-coding RNAs, which can have the same function as microRNA (miRNA) sponges, as regulators of splicing and transcription, and as interactors with RNA-binding proteins (RBPs). Therefore, circRNAs have been investigated as specific targets for diagnostic and prognostic detection of CRC. These non-coding RNAs are also linked to metastasis, proliferation, differentiation, migration, angiogenesis, apoptosis, and drug resistance, illustrating the importance of understanding their involvement in the molecular mechanisms of development and progression of CRC. In this review, we present a detailed summary of recent findings relating to the dysregulation of circRNAs and their potential role in CRC.

scholarly journals Characterizing Expression and Regulation of Gamma-Herpesviral Circular RNAs

2021 ◽  
Vol 12 ◽  
Author(s):  
Takanobu Tagawa ◽  
Daniel Oh ◽  
Jerico Santos ◽  
Sarah Dremel ◽  
Guruswamy Mahesh ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Rna Binding ◽  
De Novo ◽  
Rna Binding Proteins ◽  
Expression Patterns ◽  
Cell Types ◽  
Positive Patient ◽  
Circular Rnas ◽  
Patient Sample

Multiple herpesviruses have been recently found to encode viral circular RNAs. Like cellular circular RNAs, these RNAs lack poly-A tails and their 5′ and 3′ ends have been joined, which confers protection from RNA exonucleases. We examined the expression patterns of circular RNAs from Kaposi’s sarcoma herpesvirus (KSHV) in various environments. We performed deep sequencing of circRNA-enriched total RNA from a KSHV-positive patient lymph node for comparison with previous circRNA-Seq results. We found that circvIRF4 is highly expressed in the KSHV-positive patient sample relative to both B cell lines and de novo infected primary vascular and lymphatic endothelial cells (LECs). Overall, this patient sample showed a viral circRNA expression pattern more similar to the pattern from B cell lines, but we also discovered new back-spliced junctions and additional viral circular RNAs in this patient sample. We validated some of these back-spliced junctions as circular RNAs with standard assays. Differential expression patterns of circular RNAs in different cell types led us to investigate what cellular factors might be influencing the ratio of viral linear mRNAs to circular RNAs. We found that repression of certain RNA-binding proteins shifted the balance between viral linear mRNAs and circular RNAs. Taken together, examining viral circular RNA expression patterns may become useful tools for discovering their functions, the regulators of their expression, and determining the stage and cell types of infection in humans.

scholarly journals Circ_0003266 sponges miR-503-5p to suppress colorectal cancer progression via regulating PDCD4 expression

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Caihong Wen ◽  
Xiaoqing Feng ◽  
Honggang Yuan ◽  
Yong Gong ◽  
Guangsheng Wang
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Progression ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Pdcd4 Expression ◽  
Novel Target

Abstract Background Circular RNAs (circRNAs) feature prominently in tumor progression. However, the biological function and molecular mechanism of circ_0003266 in colorectal cancer (CRC) require further investigation. Methods Circ_0003266 expression in 46 pairs CRC tissues / adjacent tissues, and CRC cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR); after circ_0003266 was overexpressed or knocked down in CRC cells, cell proliferation, apoptosis, migration, and invasion were evaluated by the cell counting kit-8 (CCK-8), flow cytometry, and Transwell assays, respectively; the interaction among circ_0003266, miR-503-5p, and programmed cell death 4 (PDCD4) was confirmed using bioinformatics analysis and dual-luciferase reporter assay; PDCD4 protein expression in CRC cells was quantified using Western blot. Results Circ_0003266 was significantly lowly expressed in CRC tissues and cell lines. Circ_0003266 overexpression markedly repressed CRC cell proliferation, migration, and invasion, and accelerated the cell apoptosis, but its overexpression promoted the malignant phenotypes of CRC cells. PDCD4 was a direct target of miR-503-5p and circ_0003266 promoted PDCD4 expression by competitively sponging miR-503-5p. Conclusion Circ_0003266 suppresses the CRC progression via sponging miR-503-5p and regulating PDCD4 expressions, which suggests that circ_0003266 may serve as a novel target for the treatment of CRC.

scholarly journals Identification of Novel RNA Binding Proteins Influencing Circular RNA Expression in Hepatocellular Carcinoma

2021 ◽  
Vol 22 (14) ◽  
pp. 7477
Author(s):  
Rok Razpotnik ◽  
Petra Nassib ◽  
Tanja Kunej ◽  
Damjana Rozman ◽  
Tadeja Režen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulatory Protein ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Bioinformatics Analyses ◽  
Published Evidence

Circular RNAs (circRNAs) are increasingly recognized as having a role in cancer development. Their expression is modified in numerous cancers, including hepatocellular carcinoma (HCC); however, little is known about the mechanisms of their regulation. The aim of this study was to identify regulators of circRNAome expression in HCC. Using publicly available datasets, we identified RNA binding proteins (RBPs) with enriched motifs around the splice sites of differentially expressed circRNAs in HCC. We confirmed the binding of some of the candidate RBPs using ChIP-seq and eCLIP datasets in the ENCODE database. Several of the identified RBPs were found to be differentially expressed in HCC and/or correlated with the overall survival of HCC patients. According to our bioinformatics analyses and published evidence, we propose that NONO, PCPB2, PCPB1, ESRP2, and HNRNPK are candidate regulators of circRNA expression in HCC. We confirmed that the knocking down the epithelial splicing regulatory protein 2 (ESRP2), known to be involved in the maintenance of the adult liver phenotype, significantly changed the expression of candidate circRNAs in a model HCC cell line. By understanding the systemic changes in transcriptome splicing, we can identify new proteins involved in the molecular pathways leading to HCC development and progression.

scholarly journals Current Understanding of Circular RNAs in Systemic Lupus Erythematosus

2021 ◽  
Vol 12 ◽  
Author(s):  
Hongjiang Liu ◽  
Yundong Zou ◽  
Chen Chen ◽  
Yundi Tang ◽  
Jianping Guo
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Complexes ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Current Understanding ◽  
Circular Rnas ◽  
Systemic Lupus

Systemic lupus erythematosus (SLE) is a common and potentially fatal autoimmune disease that affects multiple organs. To date, its etiology and pathogenesis remains elusive. Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNAs with covalently closed loop structure. Growing evidence has demonstrated that circRNAs may play an essential role in regulation of gene expression and transcription by acting as microRNA (miRNA) sponges, impacting cell survival and proliferation by interacting with RNA binding proteins (RBPs), and strengthening mRNA stability by forming RNA-protein complexes duplex structures. The expression patterns of circRNAs exhibit tissue-specific and pathogenesis-related manner. CircRNAs have implicated in the development of multiple autoimmune diseases, including SLE. In this review, we summarize the characteristics, biogenesis, and potential functions of circRNAs, its impact on immune responses and highlight current understanding of circRNAs in the pathogenesis of SLE.

scholarly journals Insights into the multifaceted role of circular RNAs: implications for Parkinson’s disease pathogenesis and diagnosis

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Epaminondas Doxakis
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Clinical Manifestations ◽  
Alpha Synuclein ◽  
Circular Rnas ◽  
Age Related ◽  
And Function ◽  
The Brain

AbstractParkinson’s disease (PD) is a complex, age-related, neurodegenerative disease whose etiology, pathology, and clinical manifestations remain incompletely understood. As a result, care focuses primarily on symptoms relief. Circular RNAs (circRNAs) are a large class of mostly noncoding RNAs that accumulate with aging in the brain and are increasingly shown to regulate all aspects of neuronal and glial development and function. They are generated by the spliceosome through the backsplicing of linear RNA. Although their biological role remains largely unknown, they have been shown to regulate transcription and splicing, act as decoys for microRNAs and RNA binding proteins, used as templates for translation, and serve as scaffolding platforms for signaling components. Considering that they are stable, diverse, and detectable in easily accessible biofluids, they are deemed promising biomarkers for diagnosing diseases. CircRNAs are differentially expressed in the brain of patients with PD, and growing evidence suggests that they regulate PD pathogenetic processes. Here, the biogenesis, expression, degradation, and detection of circRNAs, as well as their proposed functions, are reviewed. Thereafter, research linking circRNAs to PD-related processes, including aging, alpha-synuclein dysregulation, neuroinflammation, and oxidative stress is highlighted, followed by recent evidence for their use as prognostic and diagnostic biomarkers for PD.

scholarly journals N-glycomic signature of stage II colorectal cancer and its association with the tumor microenvironment

2020 ◽  
pp. mcp.RA120.002215
Author(s):  
Fanny Boyaval ◽  
René Van Zeijl ◽  
Hans Dalebout ◽  
Stephanie Holst ◽  
Gabi W. van Pelt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mass Spectrometry Imaging ◽  
Stage Ii ◽  
Cell Populations ◽  
Invasive Front ◽  
Tissue Samples ◽  
Sample Group ◽  
Patients At Risk ◽  
Stage Ii Colorectal Cancer ◽  
High Mannose

The choice for adjuvant chemotherapy in stage II colorectal cancer (CRC) is controversial as many patients are cured by surgery alone and it is difficult to identify patients with high-risk of recurrence of the disease. There is a need for better stratification of this group of patients. Mass spectrometry imaging could identify patients at risk. We report here the N-glycosylation signatures of the different cell populations in a group of stage II CRC tissue samples. The cancer cells, compared to normal epithelial cells, have increased levels of sialylation and high-mannose glycans, as well as decreased levels of fucosylation and highly branched N-glycans. When looking at the interface between cancer and its microenvironment, it seems that the cancer N-glycosylation signature spreads into the surrounding stroma at the invasive front of the tumor. This finding was more outspoken in patients with a worse outcome within this sample group.

scholarly journals Circular RNA circCCDC66 Contributes to Malignant Phenotype of Osteosarcoma by Sponging miR-338-3p to Upregulate the Expression of PTP1B

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Deng Xiang ◽  
Yugang Li ◽  
Yanshui Lin
Keyword(s):  
Cell Proliferation ◽  
Molecular Mechanism ◽  
Cell Lines ◽  
Rapid Development ◽  
Circular Rna ◽  
Molecular Medicine ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Tissue Samples

In recent years, the mechanism of cancer research has become hotspots of life science and medicine, especially due to the rapid development of molecular medicine and bioinformatics research. Similarly, the molecular mechanism also has received increasing attention in osteosarcoma (OS) research. Also, a considerable amount of research confirmed that circular RNAs (circRNAs) could regulate cancer cell growth and metastasis. This study aimed to explore the effect of a circRNA, circCCDC66, on OS and reveal its potential molecular mechanism. High circCCDC66 expression level was found in OS patient-derived tissue samples and OS cell lines by qRT-PCR. The abilities cell proliferation and metastatic of U2OS and SW1353 cells were then assessed by Cell Counting Kit-8 and transwell assay, respectively. The interaction between circCCDC66 and its target miRNAs were verified by the dual-luciferase reporter assay. Through functional experiments, we found that circCCDC66 knockdown promoted the inhibition of cell proliferation and metastatic of OS cell lines. From mechanistic perspective, circCCDC66 upregulated PTP1B by sponging miR-338-3p. Collectively, our findings demonstrated that circCCDC66 contributed to malignant behaviors of OS cells by miR-338-3p/PTP1B pathway, which suggested circCCDC66/miR-338-3p/PTP1B axis might be a potential therapeutic target.

scholarly journals Down-Regulation of MicroRNA-214 Contributed to the Enhanced Mitochondrial Transcription Factor A and Inhibited Proliferation of Colorectal Cancer Cells

2018 ◽  
Vol 49 (2) ◽  
pp. 545-554 ◽  
Author(s):  
Kaiming Wu ◽  
Jun Ma ◽  
Yanfeng Zhan ◽  
Kuanzhi Liu ◽  
Ziyin Ye ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Transcription Factor ◽  
Cell Lines ◽  
Nuclear Translocation ◽  
Malignant Tumors ◽  
Down Regulation ◽  
Mitochondrial Transcription ◽  
Tissue Samples ◽  
Mitochondrial Transcription Factor ◽  
Mitochondrial Transcription Factor A

Background/Aims: Colon cancer, also known as colorectal cancer (CRC), is one of the most common malignant tumors globally. Although significant advances have been made for developing novel therapeutics, the mechanisms of progression of colorectal cancer are still poorly understood. Methods: In this study, we identified down-regulation of microRNA-214 (miR-214) as the contributing factor for CRC. Mitochondrial transcription factor A (TFAM) and miR-214 expression in tumor samples from colorectal cancer patients and cancer cell lines were examined by reverse transcription and real-Time PCR (qPCR) or Western Blotting. Results: Our data demonstrated that miR-214 was significantly down-regulated in the tissue samples from CRC patients as well as CRC derived cell lines. TFAM overexpression was also observed in CRC patients and identified as a target for miR-214. Knockdown of TFAM by miR-214 mimics significantly inhibited the proliferation of CRC cell lines. Also, down-regulation of TFAM inhibited nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) nuclear translocation and the expression of NF-κB depended genes. Conclusion: In conclusion, our data suggested that down-regulation of MiR-214 contributed to the enhanced TFAM expression and decreased proliferation of CRC cells.

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