CircRNAs: a regulator of cellular stress

Fischer, Joseph W.; Leung, Anthony K.L.

doi:10.1080/10409238.2016.1276882

Cited by 141 publications

(133 citation statements)

References 104 publications

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“…CircRNAs have been postulated to function as microRNA sponges (Hansen et al, 2013, 2011; Memczak et al, 2013), in cell-to-cell information transfer (Lasda and Parker, 2016), as templates for translation (Legnini et al, 2017; Pamudurti et al, 2017; Yang et al, 2017), or memory due to their extraordinary stability (Fischer and Leung, 2017). However, the ability of exogenous circRNA to activate immune response or inhibit viral infection has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Sensing Self and Foreign Circular RNAs by Intron Identity

et al. 2017

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SUMMARY Circular RNAs (circRNAs) are single-stranded RNAs that are joined head to tail with largely unknown functions. Here we show that transfection of purified in vitro generated circRNA into mammalian cells led to potent induction of innate immunity genes and confers protection against viral infection. The nucleic acid sensor RIG-I is necessary to sense foreign circRNA, and RIG-I and foreign circRNA co-aggregate in cytoplasmic foci. CircRNA activation of innate immunity is independent of a 5′ triphosphate, double-stranded RNA structure, or the primary sequence of the foreign circRNA. Instead, self-nonself discrimination depends on the intron that programs the circRNA. Use of a human intron to express a foreign circRNA sequence abrogates immune activation, and mature human circRNA is associated with diverse RNA binding proteins reflecting its endogenous splicing and biogenesis. These results reveal innate immune sensing of circRNA and highlight introns—the predominant output of mammalian transcription—as arbiters of self-nonself identity.

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Section: Introductionmentioning

confidence: 99%

Sensing Self and Foreign Circular RNAs by Intron Identity

et al. 2017

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“…CircRNAs are generally considerate as non-coding RNA, although Pamudurti et al found some specific circRNAs can also transcribed into proteins [7]. Increasing evidence reveals that circRNAs have key functions in regulating various physiological and pathological processes [8, 9]. It has been demonstrated that circRNAs could serve as competing endogenous RNAs (ceRNAs) to inhibit the activity of microRNAs (miRNAs) [10].…”

Section: Introductionmentioning

confidence: 99%

Microarray Expression Profile of Circular RNAs in Peripheral Blood Mononuclear Cells from Active Tuberculosis Patients

Huang

Yao²,

et al. 2018

Cell Physiol Biochem

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Background/Aims: Dysregulated expression of circular RNAs (circRNAs) was demonstrated to be implicated in many diseases. Here, we aimed to determine circRNA profile in peripheral blood mononuclear cells (PBMCs) from active tuberculosis (TB) patients to identify novel biomarkers for TB. Methods: Expression profile of circRNAs in PBMCs from 3 active pulmonary TB patients and 3 healthy controls were analyzed by microarray assay. Six circRNAs were selected for validation using real time-quantitative PCR (qRT-PCR) in 40 TB patients and 40 control subjects. Receiver operating characteristic (ROC) curve was constructed to evaluate their values in TB diagnosis. Hsa_circRNA_001937 was chosen for further evaluation in an independent cohort consisting of 115 TB, 40 pneumonia, 40 COPD, 40 lung cancer patients and 90 control subjects. An eight-month follow up was performed in 20 newly diagnosed TB patients to investigate the expression change of hsa_circRNA_001937 after chemotherapy. Results: We revealed and confirmed that a number of circRNAs were dysregulated in TB patients. Of the six studied physio circRNAs, the levels of hsa_circRNA_001937, hsa_circRNA_009024 and hsa_ circRNA_005086 were significantly elevated and hsa_circRNA_102101, hsa_circRNA_104964 and hsa_circRNA_104296 were significantly reduced in PBMCs from TB patients as compared to healthy controls. ROC curve analysis suggested that hsa_circRNA_001937 has the largest area under the curve (AUC = 0.873, P<0.001). Hsa_circRNA_001937 was significantly increased in patients with TB compared with patients with pneumonia, COPD and lung cancer. Hsa_ circRNA_001937 was correlated with TB severity (r = 0.4053, P = 0.010) and its expression significantly decreased after treatment. Conclusion: This study identified a set of deregulated circRNAs in active TB PBMCs, our data also suggest that hsa_circRNA_001937 can be used as a potential diagnostic biomarker of TB.

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“…But recently, mounting studies have shown that circRNAs play important roles and serve various functions in nervous system, carcinogenesis, cardiovascular diseases, immunomodulation and metabolic disorder [5][6][7][8]. CircRNA could regulates target gene or protein expression in various manners [9]: function as microRNA (miRNA) sponges to show miRNA inhibition effect by competing endogenous RNA (ceRNA) [10], interfere with their parental genes by modulation of alternative splicing or transcription [11], and interact with RNA-binding proteins (RBPs) as scaffolds for the assembly of protein complexes [12].…”

Section: Introductionmentioning

confidence: 99%

CircRNA circ-0110102 Function as Anti-oncogenic Gene in Hepatocellular Carcinoma through Modulating miR-580-5p/CCL2 Pathway

Wang¹,

Wei²,

Xu³

et al. 2020

Preprint

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Background Circular RNAs (circRNAs) have been shown to have critical regulatory roles in tumor biology, whereas their contributions in hepatocellular carcinoma (HCC) still remains enigmatic. The purpose of this study was to investigate the molecular mechanisms involved in hsa_circ_0110102 in the occurrence and development of HCC. Results hsa_circ_0110102 was significantly down-regulated in HCC cell lines and tissues, low hsa_circ_0110102 expression levels were associated with poor prognosis. Knockdown hsa_circ_0110102 significantly inhibited cell proliferation, migration and invasion. In addition, the interaction between hsa_circ_0110102 and miR-580-5p was predicted and verified by luciferase assay and RNA pull-down, indicating that hsa_circ_0110102 function as sponge of miR-580-5p. Moreover, miR-580-5p which could directly bind to the 3’-UTR of CCL2 and induce its expression, then active the COX-2/PGE2 pathway in macrophage via FoxO1 in p38 MAPK dependent manner. Furthermore, the Δ256 mutant of FoxO1 showed no activation effect. These results concluded that hsa_circ_0110102 act as a sponge for miR-580-5p and decreased CCL2 secretion in HCC cells, then inhibits pro-inflammatory cytokine release from activated macrophage by regulating the COX-2/PGE2 pathway. Conclusions These results indicating that hsa_circ_0110102 serves as a potential prognostic predictor or therapeutic target for HCC.

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CircRNAs: a regulator of cellular stress

Cited by 141 publications

References 104 publications

Sensing Self and Foreign Circular RNAs by Intron Identity

Sensing Self and Foreign Circular RNAs by Intron Identity

Microarray Expression Profile of Circular RNAs in Peripheral Blood Mononuclear Cells from Active Tuberculosis Patients

CircRNA circ-0110102 Function as Anti-oncogenic Gene in Hepatocellular Carcinoma through Modulating miR-580-5p/CCL2 Pathway

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