circCsnk1g3- and circAnkib1-regulated interferon responses in sarcoma promote tumorigenesis by shaping the immune microenvironment

Piras, Roberta; Ko, Emily Y.; Barrett, Connor; Simone, Marco De; Lin, Xianzhi; Broz, Marina T; Tessaro, Fernando Henrique Galvão; Castillo-Martín, Mireia; Cordon‐Cardo, Carlos; Goodridge, Helen S.; Vizio, Dolores Di; Batish, Mona; Lawrenson, Kate; Chen, Y. Grace; Chan, Keith S.; Guarnerio, Jlenia

doi:10.1038/s41467-022-34872-8

Cited by 10 publications

(6 citation statements)

References 56 publications

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“…Host linear genes of exon‐derived circRNAs were generated using the same pre‐mRNA. [ 25 ] We hypothesized that HIF1A activates the transcription of the host linear gene, leading to an abundance of circPLEKHM1 in exosomes under hypoxic conditions. Indeed, the expression level of circPLEKHM1 is highly correlated with that of its host linear gene PLEKHM1 (Figure S1G , Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

Hypoxic Exosomal circPLEKHM1‐Mediated Crosstalk between Tumor Cells and Macrophages Drives Lung Cancer Metastasis

Wang,

Jin

et al. 2024

Advanced Science

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Intercellular communication often relies on exosomes as messengers and is critical for cancer metastasis in hypoxic tumor microenvironment. Some circular RNAs (circRNAs) are enriched in cancer cell‐derived exosomes, but little is known about their ability to regulate intercellular communication and cancer metastasis. Here, by systematically analyzing exosomes secreted by non‐small cell lung cancer (NSCLC) cells, a hypoxia‐induced exosomal circPLEKHM1 is identified that drives NSCLC metastasis through polarizing macrophages toward to M2 type. Mechanistically, exosomal circPLEKHM1 promoted PABPC1‐eIF4G interaction to facilitate the translation of the oncostatin M receptor (OSMR), thereby promoting macrophage polarization for cancer metastasis. Importantly, circPLEKHM1‐targeted therapy significantly reduces NSCLC metastasis in vivo. circPLEKHM1 serves as a prognostic biomarker for metastasis and poor survival in NSCLC patients. This study unveils a new circRNA‐mediated mechanism underlying how cancer cells crosstalk with macrophages within the hypoxic tumor microenvironment to promote metastasis, highlighting the importance of exosomal circPLEKHM1 as a prognostic biomarker and therapeutic target for lung cancer metastasis.

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Section: Resultsmentioning

confidence: 99%

Hypoxic Exosomal circPLEKHM1‐Mediated Crosstalk between Tumor Cells and Macrophages Drives Lung Cancer Metastasis

Wang,

Jin

et al. 2024

Advanced Science

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“…A similar protective interaction has also been recently described for circCSNK1G3, which harbors strong TDMD-like sites for Mir-181b/d. However, despite increased miR-181 levels, circCSNK1G3 expression resulted in an overall decrease in target gene repression (Piras et al, 2022). In the case of circRERE, our data currently supports a stabilizing interaction between circRERE and miR-128-3p, similar to what was observed for Cdr1as and miR-7.…”

Section: Discussionmentioning

confidence: 99%

A functional screen uncovers circular RNAs regulating excitatory synaptogenesis in hippocampal neurons

Kelly,

Bicker,

Winterer

et al. 2024

Preprint

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Circular RNAs (circRNAs) are an expanding class of largely unexplored RNAs which are prominently enriched in the mammalian brain. Here, we systematically interrogated their role in excitatory synaptogenesis of rat hippocampal neurons using RNA interference. Thereby, we identified seven circRNAs as negative regulators of excitatory synapse formation, many of which contain high-affinity microRNA binding sites. Knockdown of one of these candidates, circRERE, surprisingly promoted the formation of electrophysiologically silent synapses. Mechanistically, circRERE knockdown resulted in a preferential upregulation of synaptic mRNAs containing binding sites for miR-128-3p because of a reduced protective interaction between miR-128-3p and circRERE. Accordingly, overexpression of circRERE rescued exaggerated synapse formation upon circRERE knockdown in a miR-128-3p binding site-specific manner. Overall, our results uncover circRERE-mediated stabilization of miR-128-3p as a novel mechanism to restrict the formation of silent excitatory synaptic co-clusters and more generally implicate circRNA-dependent microRNA regulation in the control of synapse development and function.

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“…In sarcoma cells, circCsnk1g3 and circAnkib1 could modulate the immune TME by regulating the expression of interferon‐related genes. At the same time, the circRNAs may control RIG‐I‐mediated pathways to inhabit pro‐inflammatory elements 175 . CircPIP5K1A could regulate interferon‐regulating factor 4 to facilitate colon cancer development 176 .…”

Section: Circrna and Gliomamentioning

confidence: 99%

“…At the same time, the circRNAs may control RIG‐I‐mediated pathways to inhabit pro‐inflammatory elements. 175 CircPIP5K1A could regulate interferon‐regulating factor 4 to facilitate colon cancer development. 176 However, relative studies on circRNA and interferon signaling in CNS tumors are currently lacking.…”

Section: Circrna and Gliomamentioning

confidence: 99%

The regulatory role and clinical application prospects of circRNA in the occurrence and development of CNS tumors

Zhang,

Wang

et al. 2023

CNS Neurosci Ther

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BackgroundCentral nervous system (CNS) tumors originate from the spinal cord or brain. The study showed that even with aggressive treatment, malignant CNS tumors have high mortality rates. However, CNS tumor risk factors and molecular mechanisms have not been verified. Due to the reasons mentioned above, diagnosis and treatment of CNS tumors in clinical practice are currently fraught with difficulties. Circular RNAs (circRNAs), single‐stranded ncRNAs with covalently closed continuous structures, are essential to CNS tumor development. Growing evidence has proved the numeral critical biological functions of circRNAs for disease progression: sponging to miRNAs, regulating gene transcription and splicing, interacting with proteins, encoding proteins/peptides, and expressing in exosomes.AimsThis review aims to summarize current progress regarding the molecular mechanism of circRNA in CNS tumors and to explore the possibilities of clinical application based on circRNA in CNS tumors.MethodsWe have summarized studies of circRNA in CNS tumors in Pubmed.ResultsThis review summarized their connection with CNS tumors and their functions, biogenesis, and biological properties. Furthermore, we introduced current advances in clinical RNA‐related technologies. Then we discussed the diagnostic and therapeutic potential (especially for immunotherapy, chemotherapy, and radiotherapy) of circRNA in CNS tumors in the context of the recent advanced research and application of RNA in clinics.ConclusionsCircRNA are increasingly proven to participate in decveloping CNS tumors. An in‐depth study of the causal mechanisms of circRNAs in CNS tomor progression will ultimately advance their implementation in the clinic and developing new strategies for preventing and treating CNS tumors.

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circCsnk1g3- and circAnkib1-regulated interferon responses in sarcoma promote tumorigenesis by shaping the immune microenvironment

Cited by 10 publications

References 56 publications

Hypoxic Exosomal circPLEKHM1‐Mediated Crosstalk between Tumor Cells and Macrophages Drives Lung Cancer Metastasis

Hypoxic Exosomal circPLEKHM1‐Mediated Crosstalk between Tumor Cells and Macrophages Drives Lung Cancer Metastasis

A functional screen uncovers circular RNAs regulating excitatory synaptogenesis in hippocampal neurons

The regulatory role and clinical application prospects of circRNA in the occurrence and development of CNS tumors

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