The functional roles of the circRNA/Wnt axis in cancer

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: May 5, 2022

Abstract CircRNAs, covalently closed noncoding RNAs, are widely expressed in a wide range of species ranging from viruses to plants mammals. CircRNAs were enriched the Wnt pathway. Aberrant pathway activation is involved development various types cancers. Accumulating evidence indicates that circRNA/Wnt axis modulates expression cancer-associated genes and then regulates cancer progression. pathway-related circRNA obviously associated with many clinical characteristics. could regulate cell biological functions by interacting Moreover, circRNAs promising potential biomarkers for diagnosis, prognosis evaluation, treatment. In our review, we summarized recent research progress on role application tumorigenesis

Language: Английский

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CircEZH2/miR-133b/IGF2BP2 aggravates colorectal cancer progression via enhancing the stability of m6A-modified CREB1 mRNA

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: June 30, 2022

Abstract Background Aberrant expression of circular RNAs (circRNAs) contributes to the initiation and progression human malignancies, but underlying mechanisms remain largely elusive. Methods High-throughput sequencing was performed screen aberrantly expressed circRNAs or miRNAs in colorectal cancer (CRC) adjacent normal tissues. A series gain- loss-of-function studies were conducted evaluate biological behaviors CRC cells. RNA pulldown, mass spectrometry, RIP, qRT-PCR, Western blot, luciferase reporter assays MeRIP-seq analysis further applied dissect detailed mechanisms. Results Here, a novel circRNA named circEZH2 (hsa_circ_0006357) screened out by RNA-seq tissues, whose is closely related clinicpathological characteristics prognosis patients. Biologically, facilitates proliferation migration cells vitro vivo. Mechanistically, interacts with m 6 reader IGF2BP2 blocks its ubiquitination-dependent degradation. Meanwhile, could serve as sponge miR-133b, resulting upregulation IGF2BP2. Particularly, circEZH2/IGF2BP2 enhances stability CREB1 mRNA, thus aggravating progression. Conclusions Our findings not only reveal pivotal roles modulating progression, also advocate for attenuating circEZH2/miR-133b/IGF2BP2/ regulatory axis combat CRC.

Language: Английский

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Circular RNAs in EMT-driven metastasis regulation: modulation of cancer cell plasticity, tumorigenesis and therapy resistance

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: May 11, 2024

The non-coding RNAs comprise a large part of human genome lack capacity in encoding functional proteins. Among various members RNAs, the circular (circRNAs) have been importance pathogenesis diseases, especially cancer. circRNAs unique closed loop structure and due to their stability, they are potential diagnostic prognostic factors increasing evidences highlighted role modulation proliferation metastasis cancer cells. On other hand, has responsible for up 90% cancer-related deaths patients, requiring more investigation regarding underlying mechanisms modulating this mechanism. EMT enhances invasion tumor cells, can trigger resistance therapy. cells demonstrate dynamic changes during including transformation from epithelial phenotype into mesenchymal increase N-cadherin vimentin levels. process is reversible its reprogramming disrupt progression aim current review understanding interaction cancers such beyond regulation affect response chemotherapy radiotherapy. onco-suppressor inhibit EMT, while tumor-promoting mediate acceleration carcinogenesis. Moreover, EMT-inducing transcription be controlled by different tumors.

Language: Английский

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HNRNPL induced circFAM13B increased bladder cancer immunotherapy sensitivity via inhibiting glycolysis through IGF2BP1/PKM2 pathway

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: Feb. 6, 2023

The response rate to immunotherapy in patients with bladder cancer (BCa) remains relatively low. Considering the stable existence and important functions tumour metabolism, role of circRNAs regulating immune escape sensitivity is receiving increasing attention.Circular RNA (circRNA) sequencing was performed on five pairs BCa samples, circFAM13B (hsa_circ_0001535) screened out because its remarkably low expression BCa. Further mRNA conducted, association glycolysis process CD8+ T cell activation confirmed. were verified by proliferation assays, cells-CD8+ co-culture assays tumorigenesis experiment among human reconstitution NOG mice. Bioinformatic analysis, RNA-protein pull down, mass spectrometry, immunoprecipitation, luciferase reporter assay fluorescence situ hybridization validate HNRNPL/circFAM13B/IGF2BP1/PKM2 cascade.Low observed BCa, it positively associated lower stage better prognosis function cells promoted circFAM13B, could attenuate reverse acidic microenvironment (TME). production granzyme B IFN-γ improved, (PD-1 antibodies) facilitated inhibition TME. Mechanistically, competitively bound KH3-4 domains IGF2BP1 subsequently reduced binding PKM2 3'UTR. Thus, stability decreased, glycolysis-induced TME inhibited. generation explored confirming whether heterogeneous nuclear ribonucleoprotein L (HNRNPL) promote formation via pre-mRNA back-splicing.HNRNPL-induced repress evasion enhance inhibiting through novel circFAM13B/IGF2BP1/PKM2 cascade. Therefore, can be used as a biomarker for guiding

Language: Английский

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Hsa_circ_0060467 promotes breast cancer liver metastasis by complexing with eIF4A3 and sponging miR-1205

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: May 9, 2023

Breast cancer (BC) is the most common and top cause of female mortality worldwide. The prognosis for patients with breast liver metastasis (BCLM) remains poor. Emerging studies suggest that circular RNAs (circRNAs) are associated progression BC. Exploration circRNAs presents a promising avenue identifying metastasis-targeting agents improving BCLM. Microarray bioinformatic analyses were used to analyze differentially expressed between three pairs BCLM primary roles hsa_circ_0060467 (circMYBL2) its target gene E2F1 in BC cells explored by multiple functional experiments. And xenograft mouse models hepatic metastases hemi-spleen illustrate function circMYBL2 vivo. intrinsic molecular mechanism involving was confirmed bioinformatics analyses, RIP assays, CHIRP luciferase reporter rescue CircMYBL2 overexpressed tissues cells. Functionally, can facilitate proliferation Mechanistically, upregulated transcription factor sponging miR-1205 complexing eukaryotic translation initiation 4A3 (eIF4A3) then facilitated epithelial-mesenchymal transition (EMT) process Our findings showed promoted tumorigenesis aggressiveness through circMYBL2/miR-1205/E2F1 circMYBL2/eIF4A3/E2F1 axes, which may provide novel targeted therapy

Language: Английский

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SSCRB: Predicting circRNA-RBP Interaction Sites Using a Sequence and Structural Feature-Based Attention Model

IEEE Journal of Biomedical and Health Informatics, Journal Year: 2024, Volume and Issue: 28(3), P. 1762 - 1772

Published: Jan. 15, 2024

The prediction of interaction sites between circular RNA (circRNA) and binding proteins (RBPs) is crucial for regulating diseases discovering new treatment approaches. Computational models have been widely used to predict circRNA-RBP due the availability genome-wide circRNA event data. However, efficiently obtaining multi-scale features improve accuracy remains a challenging problem. In this study, we propose SSCRB, lightweight model predicting sites. Our extracts both sequence structural incorporates through attention mechanism. Furthermore, develop an ensemble by combining multiple submodels enhance predictive performance generalizability. We evaluate SSCRB on 37 datasets compare it with other state-of-the-art methods. average AUC 97.66%, demonstrating its efficiency robustness. outperforms methods in terms while requiring significantly fewer computational resources.

Language: Английский

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POSTAR: a platform for exploring post-transcriptional regulation coordinated by RNA-binding proteins

Nucleic Acids Research, Journal Year: 2016, Volume and Issue: 45(D1), P. D104 - D114

Published: Sept. 29, 2016

We present POSTAR (http://POSTAR.ncrnalab.org), a resource of POST-trAnscriptional Regulation coordinated by RNA-binding proteins (RBPs). Precise characterization post-transcriptional regulatory maps has accelerated dramatically in the past few years. Based on new studies and resources, supplies largest collection experimentally probed (∼23 million) computationally predicted (approximately 117 RBP binding sites human mouse transcriptomes. annotates every transcript its using extensive information regarding various molecular events (e.g., splicing, editing, modification), RNA secondary structures, disease-associated variants, gene expression function. Moreover, provides friendly, multi-mode, integrated search interface, which helps users to connect multiple with events, phenotypes, diseases. our platform, we were able obtain novel insights into regulation, such as putative association between CPSF6 binding, structural domains, Li-Fraumeni syndrome SNPs. In summary, represents an early effort systematically annotate explore roles RBPs

Language: Английский

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Circular RNAs in cancer: new insights into functions and implications in ovarian cancer

Journal of Ovarian Research, Journal Year: 2019, Volume and Issue: 12(1)

Published: Sept. 3, 2019

Circular RNAs (circRNAs) are a class of long non-coding (lncRNAs) which have circular and closed loop structure. They ubiquitous, stable, conserved diverse RNA molecules with range activities such as translation splicing regulation, able to interacting RNA-binding proteins specially miRNA sponge. The expression patterns the circRNAs exhibited tissue specificity also, step stage specificity. Accumulating evidences approved critical role in many cancers ovarian cancer. Given that these exert their effects through multiple cellular molecular mechanisms (i.e., angiogenesis, apoptosis, growth, metastasis) involved cancer pathogenesis, RNAs, particular, act by controlling cell proliferation cancer, so that, it has been shown deregulation is associated initiation progression Therefore, they attractive introduced them biomarkers. Moreover, could be used new therapeutic candidates for developing novel treatment strategies. Here, first time, we provided comprehensive review on recent knowledge pathological roles

Language: Английский

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CircRNAs: biogenesis, functions, and role in drug-resistant Tumours

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: Aug. 5, 2020

Abstract Targeted treatment, which can specifically kill tumour cells without affecting normal cells, is a new approach for therapy. However, tend to acquire resistance targeted drugs during treatment. Circular RNAs (circRNAs) are single-stranded RNA molecules with unique structures and important functions. With the development of sequencing technology, circRNAs have been found be widespread in tumour-resistant play regulatory roles. In this review, we present latest advances circRNA research summarize various mechanisms underlying their regulation. Moreover, review role chemotherapeutic tumours explore clinical value regulation treating resistance.

Language: Английский

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CircDLST promotes the tumorigenesis and metastasis of gastric cancer by sponging miR-502-5p and activating the NRAS/MEK1/ERK1/2 signaling

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: April 5, 2019

Accumulating evidence shows that, the dysregulation of circular RNAs (circRNAs) is associated with progression multiple malignancies. But, underlying mechanisms by which has_circ_0032627 (circDLST) contributed to gastric cancer (GC) remain undocumented. The expression and cellular localization circDLST its association clinicopathological characteristics prognosis in patients GC was analysed using fluorescence situ hybridization. Gain- loss-of-function experiments as well a subcutaneous xenograft tumor model liver metastasis from orthotopic implantation tissues were conducted assess role cells. CircDLST specific binding miR-502-5p confirmed dual luciferase gene report, RNA immunoprecipitation (RIP) assays RIP-miRNA profiling. qRT-PCR Western blot analysis used detect effects on miR-502-5p-mediated NRAS/MEK1/ERK1/2 signaling levels dramatically elevated compared adjacent normal tissues, acted an independent prognostic factor poor survival GC. Knockdown inhibited cell viability, colony formation, DNA synthesis, invasion vitro vivo, whereas overexpression had opposite effects. Furthermore, co-localized cytoplasm cells, sponge miR-502-3p abrogated promoting inactivating promotes tumorigenesis cells sponging activate signaling.

Language: Английский

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