Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape

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

Published: Jan. 15, 2019

Tumor immune escape is an important strategy of tumor survival. There are many mechanisms 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 component can inhibit the activation T lymphocytes and enhance tolerance cells, thereby achieving escape. Therefore, targeting PD-L1/PD-1 attractive for cancer treatment; however, therapeutic effectiveness remains poor. This situation requires gaining deeper understanding complex varied molecular factors driving expression pathway. In this review, we summarize regulation microenvironment their roles mediating Overall, evidence accumulated to date suggests that induction PD-L1 by inflammatory may be one most affecting efficiency blocking.

Language: Английский

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Functions of N6-methyladenosine and its role in cancer

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

Published: Dec. 1, 2019

N6-methyladenosine (m6A) is methylation that occurs in the N6-position of adenosine, which most prevalent internal modification on eukaryotic mRNA. Accumulating evidence suggests m6A modulates gene expression, thereby regulating cellular processes ranging from cell self-renewal, differentiation, invasion and apoptosis. M6A installed by methyltransferases, removed demethylases recognized reader proteins, regulate RNA metabolism including translation, splicing, export, degradation microRNA processing. Alteration levels participates cancer pathogenesis development via expression tumor-related genes like BRD4, MYC, SOCS2 EGFR. In this review, we elaborate recent advances research enzymes. We also highlight underlying mechanism progression. Finally, review corresponding potential targets therapy.

Language: Английский

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Circular RNA circNRIP1 acts as a microRNA-149-5p sponge to promote gastric cancer progression via the AKT1/mTOR pathway

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

Published: Feb. 4, 2019

CircRNA has emerged as a new non-coding RNA that plays crucial roles in tumour initiation and development. 'MiRNA sponge' is the most reported role played by circRNAs many tumours. The AKT/mTOR axis classic signalling pathway cancers sustains energy homeostasis through production activities, such Warburg effect, blocks catabolic autophagy. Additionally, exerts positive effect on EMT, which promotes metastasis. We detected higher circNRIP1 expression gastric cancer performing RNA-seq analysis. verified promotor of cells series biological function assays. then used pull-down assay dual-luciferase reporter to identify downstream miR-149-5p circNRIP1. Western blot analysis immunofluorescence assays were performed demonstrate circNRIP1-miR-149-5p-AKT1/mTOR responsible for altered metabolism GC adopted co-culture system trace transmission via exosomal communication RIP experiments determine quaking regulates expression. Finally, we confirmed suppressor microRNA-133a-3p vivo PDX mouse models. discovered knockdown successfully blocked proliferation, migration, invasion level AKT1 cells. MiR-149-5p inhibition phenocopied overexpression cells, malignant behaviours Moreover, it was proven can be transmitted between promoted metastasis vivo. also demonstrated promote transcription. In final step, proved sponges affect eventually acts GC.

Language: Английский

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Circular RNAs: Promising Biomarkers for Human Diseases

EBioMedicine, Journal Year: 2018, Volume and Issue: 34, P. 267 - 274

Published: Aug. 1, 2018

Circular RNA (circRNA) is a group of endogenous noncoding characterized by covalently closed cyclic structure lacking poly-adenylated tails. Recent studies have suggested that circRNAs play crucial role in regulating gene expression acting as microRNA sponge, binding protein sponge and translational regulator. CircRNAs become research hotspot because their close association with the development diseases. Some are reportedly expressed tissue- stage-specific manner. Furthermore, due to other features including stability, conservation high abundance body fluids, believed be potential biomarkers for various In present review, we provide current understanding biogenesis regulatory mechanisms circRNAs, summarize recent on diagnostic prognostic biomarkers, highlight major advantages limitations novel based existing knowledge.

Language: Английский

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Circular RNA-protein interactions: functions, mechanisms, and identification

Theranostics, Journal Year: 2020, Volume and Issue: 10(8), P. 3503 - 3517

Published: Jan. 1, 2020

Circular RNAs (circRNAs) are covalently closed, endogenous with no 5′ end caps or 3′ poly(A) tails.These expressed in tissue-specific, cell-specific, and developmental stage-specific patterns.The biogenesis of circRNAs is now known to be regulated by multiple specific factors; however, were previously thought insignificant byproducts splicing errors.Recent studies have demonstrated their activity as microRNA (miRNA) sponges well protein sponges, decoys, scaffolds, recruiters, some even act translation templates pathophysiological processes.CircRNAs bind sequester proteins appropriate subcellular positions, they participate modulating certain protein-protein protein-RNA interactions.Conversely, several play an indispensable role the life cycle from degradation.However, exact mechanisms these interactions between remain unknown.Here, we review current knowledge regarding circRNA-protein methods used identify characterize interactions.We also summarize new insights into potential underlying interactions.

Language: Английский

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The role of microenvironment in tumor angiogenesis

Journal of Experimental & Clinical Cancer Research, Journal Year: 2020, Volume and Issue: 39(1)

Published: Sept. 30, 2020

Abstract Tumor angiogenesis is necessary for the continued survival and development of tumor cells, plays an important role in their growth, invasion, metastasis. The microenvironment—composed surrounding secreted cytokines—provides a conducive environment growth tumors. Different components microenvironment can regulate development. In this review, we have discussed regulatory angiogenesis. High expression angiogenic factors inflammatory cytokines microenvironment, as well hypoxia, are presumed to be reasons poor therapeutic efficacy current anti-angiogenic drugs. A combination drugs antitumor or hypoxia inhibitors might improve outcome.

Language: Английский

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Emerging role of tumor-related functional peptides encoded by lncRNA and circRNA

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

Published: Feb. 4, 2020

Abstract Non-coding RNAs do not encode proteins and regulate various oncological processes. They are also important potential cancer diagnostic prognostic biomarkers. Bioinformatics translation omics have begun to elucidate the roles modes of action functional peptides encoded by ncRNA. Here, recent advances in long non-coding RNA (lncRNA) circular (circRNA)-encoded small compiled synthesized. We introduce both computational analytical methods used forecast prospective ncRNAs encoding oncologically oligopeptides. present numerous specific lncRNA circRNA-encoded their cancer-promoting or cancer-inhibiting molecular mechanisms. This information may expedite discovery, development, optimization novel efficacious diagnostic, therapeutic, protein-based tools derived from RNAs. The role ncRNA-encoding has promising application perspectives challenges research. aim this review is provide a theoretical basis relevant references, which promote discovery more ncRNAs, further develop anticancer therapeutic targets, as well markers.

Language: Английский

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Circbank: a comprehensive database for circRNA with standard nomenclature

RNA Biology, Journal Year: 2019, Volume and Issue: 16(7), P. 899 - 905

Published: April 25, 2019

Circular RNAs (circRNAs) represent a new type of regulatory RNA which forms covalently closed continuous loop from back-splicing events, process in the downstream 5' splice site and 3' are linked. Emerging evidence indicates that circRNAs exert layer transcriptional post-transcriptional regulation gene expression. However, there is no standard nomenclature circRNA, although study has exploded past few years. Here we present circbank ( www.circbank.cn ), comprehensive database for human circRNAs, where novel naming system based on host genes was implemented. In addition to system, collected other five features including miRNA binding site, conservation m6A modification mutation protein-coding potential circRNAs. Circbank publicly available allows users query, browse download with all six provided, different search criteria. The may serve as resource facilitate research function

Language: Английский

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Circular RNAs in Cancer: emerging functions in hallmarks, stemness, resistance and roles as potential biomarkers

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

Published: April 18, 2019

Circular RNAs (circRNAs) are a class of RNA molecules with closed loops and high stability. CircRNAs abundantly expressed in eukaryotic organisms exhibit both location- step-specificity. In recent years, circRNAs attracting considerable research attention attributed to their possible contributions gene regulation through variety actions, including sponging microRNAs, interacting RNA-binding proteins, regulating transcription splicing, protein translation. Growing evidence has revealed that play critical roles the development progression diseases, especially cancers. Without doubt, expanding our understanding will enrich knowledge cancer provide new opportunities for therapy. this review, we an overview characteristics, functions functional mechanisms circRNAs. particular, summarize current regarding hallmarks, stemness, resistance cancer, as well possibility biomarkers cancer.

Language: Английский

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Role of metabolism in cancer cell radioresistance and radiosensitization methods

Journal of Experimental & Clinical Cancer Research, Journal Year: 2018, Volume and Issue: 37(1)

Published: April 23, 2018

Radioresistance is a major factor leading to the failure of radiotherapy and poor prognosis in tumor patients. Following application radiotherapy, activity various metabolic pathways considerably changes, which may result development resistance radiation. Here, we discussed relationships between radioresistance mitochondrial glucose pathways, aiming elucidate interplay cell metabolism resistance. In this review, additionally summarized potential therapeutic targets pathways. The aim review was provide theoretical basis relevant references, lead improvement sensitivity prolong survival cancer

Language: Английский

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