Hsa_circ_0020397 regulates colorectal cancer cell viability, apoptosis and invasion by promoting the expression of the miR-138 targets TERT and PD-L1.
TL;DR: Findings support the role of circRNA in CRC pathogenesis by suggesting that hsa_circ_0020397 can regulate CRC cell viability, apoptosis and invasion by promoting the expression of miR‐138 target genes.
About: This article is published in Cell Biology International.The article was published on 2017-09-01. It has received 193 citations till now.
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TL;DR: Overall, the evidence accumulated to date suggests that induction of PD-L1 by inflammatory factors in the tumor microenvironment may be one of the most important factors affecting the therapeutic efficiency of PD -L1/PD-1 blocking.
Abstract: Tumor immune escape is an important strategy of tumor survival. There are many mechanisms of tumor immune escape, including immunosuppression, which has become a research hotspot in recent years. The programmed death ligand-1/programmed death-1 (PD-L1/PD-1) signaling pathway is an important component of tumor immunosuppression, which can inhibit the activation of T lymphocytes and enhance the immune tolerance of tumor cells, thereby achieving tumor immune escape. Therefore, targeting the PD-L1/PD-1 pathway is an attractive strategy for cancer treatment; however, the therapeutic effectiveness of PD-L1/PD-1 remains poor. This situation requires gaining a deeper understanding of the complex and varied molecular mechanisms and factors driving the expression and activation of the PD-L1/PD-1 signaling pathway. In this review, we summarize the regulation mechanisms of the PD-L1/PD-1 signaling pathway in the tumor microenvironment and their roles in mediating tumor escape. Overall, the evidence accumulated to date suggests that induction of PD-L1 by inflammatory factors in the tumor microenvironment may be one of the most important factors affecting the therapeutic efficiency of PD-L1/PD-1 blocking.
676 citations
Cites background from "Hsa_circ_0020397 regulates colorect..."
...In colorectal cancer, the circRNA molecule Hsa_circ_0020397 was shown to inhibit the activity of miR-138 via an RNA sponge effect, thus promoting the expression of PD-L1 [172]....
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TL;DR: Current knowledge of the miRNA-circRNA interaction and mechanisms that influence gene expression are summarized.
Abstract: Majority of RNAs expressed in animal cells lack protein-coding ability. Unlike other cellular RNAs, circular (circ)RNAs include a large family of noncoding (nc)RNAs that lack the 5′ or 3′ ends. The improvements in high-throughput RNA sequencing and novel bioinformatics tools have led to the identification of thousands of circRNAs in various organisms. CircRNAs can regulate gene expression by influencing the transcription, the mRNA turnover, and translation by sponging RNA-binding proteins and microRNAs. Given the broad impact of circRNA on miRNA activity, there is huge interest in understanding the impact of miRNA sponging by circRNA on gene regulation. In this review, we summarize our current knowledge of the miRNA-circRNA interaction and mechanisms that influence gene expression.
670 citations
TL;DR: Although their exact roles and mechanisms of gene regulation remain to be clarified, circRNAs have potential applications as disease biomarkers and novel therapeutic targets.
551 citations
TL;DR: The characteristics, functions, and mechanisms of action of circRNAs in cancer are highlighted and an overview of recent progress in the circRNA field is provided and future application of circ RNAs as cancer biomarkers and novel therapeutic targets is provided.
Abstract: Circular RNAs (circRNAs) are a class of single-stranded closed RNA molecules that are formed by precursor mRNA back-splicing or skipping events of thousands of genes in eukaryotes as covalently closed continuous loops. High-throughput sequencing and bioinformatics approaches have uncovered the broad expression of circRNAs across species. Their high stability, abundance, and evolutionary conservation among species points to their distinct properties and diverse cellular functions as efficient microRNAs and protein sponges; they also play important roles in modulating transcription and splicing. Additionally, most circRNAs are aberrantly expressed in pathological conditions and in a tissue-specific manner such as development and progression of cancer. Herein, we highlight the characteristics, functions, and mechanisms of action of circRNAs in cancer; we also provide an overview of recent progress in the circRNA field and future application of circRNAs as cancer biomarkers and novel therapeutic targets.
290 citations
TL;DR: The current state of knowledge regarding circRNAs, their synthesis, function, and association with cancer are considered, and some of the challenges that remain to be resolved are reviewed if this emerging class of RNAs are really to become useful in the clinic.
264 citations
References
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TL;DR: Overall cancer incidence trends are stable in women, but declining by 3.1% per year in men, much of which is because of recent rapid declines in prostate cancer diagnoses, and brain cancer has surpassed leukemia as the leading cause of cancer death among children and adolescents.
Abstract: Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the National Cancer Institute (Surveillance, Epidemiology, and End Results [SEER] Program), the Centers for Disease Control and Prevention (National Program of Cancer Registries), and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics. In 2016, 1,685,210 new cancer cases and 595,690 cancer deaths are projected to occur in the United States. Overall cancer incidence trends (13 oldest SEER registries) are stable in women, but declining by 3.1% per year in men (from 2009-2012), much of which is because of recent rapid declines in prostate cancer diagnoses. The cancer death rate has dropped by 23% since 1991, translating to more than 1.7 million deaths averted through 2012. Despite this progress, death rates are increasing for cancers of the liver, pancreas, and uterine corpus, and cancer is now the leading cause of death in 21 states, primarily due to exceptionally large reductions in death from heart disease. Among children and adolescents (aged birth-19 years), brain cancer has surpassed leukemia as the leading cause of cancer death because of the dramatic therapeutic advances against leukemia. Accelerating progress against cancer requires both increased national investment in cancer research and the application of existing cancer control knowledge across all segments of the population.
14,664 citations
"Hsa_circ_0020397 regulates colorect..." refers background in this paper
...The incidence and mortality of CRC in China continues to increase (Chen et al., 2016a; Siegel et al., 2016)....
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TL;DR: Many of the estimated cancer cases and deaths can be prevented through reducing the prevalence of risk factors, while increasing the effectiveness of clinical care delivery, particularly for those living in rural areas and in disadvantaged populations.
Abstract: With increasing incidence and mortality, cancer is the leading cause of death in China and is a major public health problem. Because of China's massive population (1.37 billion), previous national incidence and mortality estimates have been limited to small samples of the population using data from the 1990s or based on a specific year. With high-quality data from an additional number of population-based registries now available through the National Central Cancer Registry of China, the authors analyzed data from 72 local, population-based cancer registries (2009-2011), representing 6.5% of the population, to estimate the number of new cases and cancer deaths for 2015. Data from 22 registries were used for trend analyses (2000-2011). The results indicated that an estimated 4292,000 new cancer cases and 2814,000 cancer deaths would occur in China in 2015, with lung cancer being the most common incident cancer and the leading cause of cancer death. Stomach, esophageal, and liver cancers were also commonly diagnosed and were identified as leading causes of cancer death. Residents of rural areas had significantly higher age-standardized (Segi population) incidence and mortality rates for all cancers combined than urban residents (213.6 per 100,000 vs 191.5 per 100,000 for incidence; 149.0 per 100,000 vs 109.5 per 100,000 for mortality, respectively). For all cancers combined, the incidence rates were stable during 2000 through 2011 for males (+0.2% per year; P = .1), whereas they increased significantly (+2.2% per year; P < .05) among females. In contrast, the mortality rates since 2006 have decreased significantly for both males (-1.4% per year; P < .05) and females (-1.1% per year; P < .05). Many of the estimated cancer cases and deaths can be prevented through reducing the prevalence of risk factors, while increasing the effectiveness of clinical care delivery, particularly for those living in rural areas and in disadvantaged populations.
13,073 citations
TL;DR: This study serves as the first functional analysis of a naturally expressed circular RNA, ciRS-7, which contains more than 70 selectively conserved miRNA target sites, and is highly and widely associated with Argonaute proteins in a miR-7-dependent manner.
Abstract: MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants. We previously identified a highly expressed circular RNA (circRNA) in human and mouse brain. Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more than 70 selectively conserved miRNA target sites, and it is highly and widely associated with Argonaute (AGO) proteins in a miR-7-dependent manner. Although the circRNA is completely resistant to miRNA-mediated target destabilization, it strongly suppresses miR-7 activity, resulting in increased levels of miR-7 targets. In the mouse brain, we observe overlapping co-expression of ciRS-7 and miR-7, particularly in neocortical and hippocampal neurons, suggesting a high degree of endogenous interaction. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. This study serves as the first, to our knowledge, functional analysis of a naturally expressed circRNA.
5,885 citations
"Hsa_circ_0020397 regulates colorect..." refers background or methods in this paper
...1 by using a previously described method (Hansen et al., 2013)....
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...Some circRNAs are rich in microRNA (miRNA) response elements and can act as competing endogenous RNAs, binding miRNAs and thereby inhibiting miRNA functions and regulating gene expression (Hansen et al., 2013; Taulli et al., 2013)....
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TL;DR: This open-label, phase 2 randomised controlled trial assessed efficacy and safety of atezolizumab versus docetaxel in previously treated NSCLC, analysed by PD-L1 expression levels on tumours and tumour-infiltrating immune cells and in the intention-to-treat population.
2,185 citations
"Hsa_circ_0020397 regulates colorect..." refers background in this paper
...Indeed, a PD-L1 blocking antibody was approved in October of 2016 for metastatic non-small cell lung cancer therapy (Fehrenbacher et al., 2016)....
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TL;DR: The results provide evidence that circular RNA produced from precursor mRNA may have a regulatory role in human cells and characterize one abundant circRNA derived from Exon2 of the HIPK3 gene, termed circHIPK3.
Abstract: Circular RNAs (circRNAs) represent a class of widespread and diverse endogenous RNAs that may regulate gene expression in eukaryotes. However, the regulation and function of human circRNAs remain largely unknown. Here we generate ribosomal-depleted RNA sequencing data from six normal tissues and seven cancers, and detect at least 27,000 circRNA candidates. Many of these circRNAs are differently expressed between the normal and cancerous tissues. We further characterize one abundant circRNA derived from Exon2 of the HIPK3 gene, termed circHIPK3. The silencing of circHIPK3 but not HIPK3 mRNA significantly inhibits human cell growth. Via a luciferase screening assay, circHIPK3 is observed to sponge to 9 miRNAs with 18 potential binding sites. Specifically, we show that circHIPK3 directly binds to miR-124 and inhibits miR-124 activity. Our results provide evidence that circular RNA produced from precursor mRNA may have a regulatory role in human cells.
1,537 citations
"Hsa_circ_0020397 regulates colorect..." refers background in this paper
...Zheng et al. (2016) found that silencing of circHIPK3, but not HIPK3 mRNA, inhibited human cell growth and that circHIPK3 binds and inhibits miR-124 directly....
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