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1.
Sci Adv ; 10(20): eadn5098, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758784

RESUMO

The scalable artificial photosynthesis composed of photovoltaic electrolysis and photothermal catalysis is limited by inefficient photothermal CO2 hydrogenation under weak sunlight irradiation. Herein, NiO nanosheets supported with Ag single atoms [two-dimensional (2D) Ni1Ag0.02O1] are synthesized for photothermal CO2 hydrogenation to achieve 1065 mmol g-1 hour-1 of CO production rate under 1-sun irradiation. This performance is attributed to the coupling effect of Ag-O-Ni sites to enhance the hydrogenation of CO2 and weaken the CO adsorption, resulting in 1434 mmol g-1 hour-1 of CO yield at 300°C. Furthermore, we integrate the 2D Ni1Ag0.02O1-supported photothermal reverse water-gas shift reaction with commercial photovoltaic electrolytic water splitting to construct a 103-m2 scale artificial photosynthesis system (CO2 + H2O → CO + H2 + O2), which achieves more than 22 m3/day of green syngas with an adjustable H2/CO ratio (0.4-3) and a photochemical energy conversion efficiency of >17%. This research charts a promising course for designing practical, natural sunlight-driven artificial photosynthesis systems.

2.
Front Psychol ; 15: 1281926, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38449754

RESUMO

There has been much debate in psycholinguistic research on whether formulaic sequences (FSs) are processed holistically or in a compositional manner. Whereas most previous studies on this issue focused on the receptive processing of FSs, few have investigated the productive processing of FSs, particularly in the second language (L2) learning context. Besides, most previous studies on L2 FSs examined learner-external FSs, or those identified by external criteria such as corpus frequency with little attention to learner-internal FSs, or psychological units perceived as wholes by learners themselves, although there might be much overlap between learner-external and learner-internal FSs. This study was designed to explore the productive processing of FSs by L2 learners from their own perspective, while taking into account the effects of L2 proficiency and topic familiarity. It made a distinction between internal FSs and purely external FSs as the primary criterion of categorizing learners' processing behaviors. Ten Chinese English learners from two proficiency levels completed two writing tasks differing in topic familiarity. Upon the completion of each task, each participant and the researcher identified the FSs separately and then distinguished internal FSs and purely external FSs (termed as assembled FSs, since they were perceived as being assembled from scratch) collectively. Next, each participant performed video stimulated recall (VSR) for the production process of each FS. The results showed that the learners' conscious processing (i.e., retrieval/assembly and integration into the text) of FSs can be categorized on two levels (lexical and syntactic). There was more holistic processing than compositional processing on the lexical level, but not on the syntactic level, indicating the learners' sizable storages of FSs and the syntactic flexibility of FSs. Furthermore, between-group differences and between-task differences were detected on two processing levels: higher-proficiency students retrieved more internal FSs and made more modifications to them than their lower-proficiency counterparts; in the familiar-topic writing, learners retrieved more internal FSs and made less modifications to them. Based on the findings, a model of L2 FS production is proposed, and pedagogical implications for the teaching of L2 FSs are provided.

3.
Aging (Albany NY) ; 16(1): 89-105, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38206646

RESUMO

Widely recognized as an essential epitranscriptomic modification, RNA N6-methyladenosine (m6A) is involved in both physiological and pathological processes. Here, we want to investigate m6A modification's potential roles in gastric cancer. Gastric cancer samples were selected from TCGA-STAD and GEO (GSE84426, GSE84433) datasets. Based on 18 regulators of m6A, m6A modification patterns were thoroughly evaluated in gastric cancer samples. Principal component analysis algorithms were used to construct the m6Ascore, using which, m6A modification features in tumor somatic mutations and immune checkpoint blockade therapy were analyzed. 34 gastric cancer samples were collected to verify the effectiveness of the m6Ascore. Here, we determined three different m6A modification patterns. m6Acluster-C modification pattern presented immune activation-associated enrichment pathways and have significant survival advantages. Then, in gastric cancer, m6Ascore could act as an independent prognostic biomarker. A significant survival benefit was exhibited in patients with high m6Ascore. Moreover, the modification signature of m6A uncovered in this study would help to predict immune checkpoint blockade therapy's responses. In conclusion, our discoveries all pointed to the fact that modification patterns of m6A were linked to the TME. Moreover, evaluation of individual tumor's m6A modification pattern will help to guide immunotherapy strategies that shows more therapeutic effects.


Assuntos
Adenina/análogos & derivados , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Inibidores de Checkpoint Imunológico , RNA , Metilação , Microambiente Tumoral
4.
Nanotechnology ; 35(5)2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37879324

RESUMO

Reverse water gas shift (RWGS) reaction is an intriguing strategy to realize carbon neutrality, however, the endothermic process usually needs high temperature that supplied by non-renewable fossil fuels, resulting in secondary energy and environmental issues. Photothermal catalysis are ideal substitutes for the conventional thermal catalysis, providing that high reaction efficiency is achievable. Two-dimensional (2D) materials are highly active as RWGS catalysts, however, their industrial application is restricted by the preparation cost. In this study, a series of 2D Co-based catalysts for photothermal RWGS reaction with tunable selectivity were prepared by self-assembly method based on cheap amylum, by integrating the 2D catalysts with our homemade photothermal device, sunlight driven efficient RWGS reaction was realized. The prepared 2D Co0.5Ce0.5Oxexhibited a full selectivity toward CO (100%) and could be heated to 318 °C under 1 kW m-2irradiation with the CO generation rate of 14.48 mmol g-1h-1, pointing out a cheap and universal method to prepare 2D materials, and zero consumption CO generation from photothermal RWGS reaction.

5.
Rep Prog Phys ; 86(10)2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37706242

RESUMO

The concept of topological energy bands and their manifestations have been demonstrated in condensed matter systems as a fantastic paradigm toward unprecedented physical phenomena and properties that are robust against disorders. Recent years, this paradigm was extended to phononic metamaterials (including mechanical and acoustic metamaterials), giving rise to the discovery of remarkable phenomena that were not observed elsewhere thanks to the extraordinary controllability and tunability of phononic metamaterials as well as versatile measuring techniques. These phenomena include, but not limited to, topological negative refraction, topological 'sasers' (i.e. the phononic analog of lasers), higher-order topological insulating states, non-Abelian topological phases, higher-order Weyl semimetal phases, Majorana-like modes in Dirac vortex structures and fragile topological phases with spectral flows. Here we review the developments in the field of topological phononic metamaterials from both theoretical and experimental perspectives with emphasis on the underlying physics principles. To give a broad view of topological phononics, we also discuss the synergy with non-Hermitian effects and cover topics including synthetic dimensions, artificial gauge fields, Floquet topological acoustics, bulk topological transport, topological pumping, and topological active matters as well as potential applications, materials fabrications and measurements of topological phononic metamaterials. Finally, we discuss the challenges, opportunities and future developments in this intriguing field and its potential impact on physics and materials science.

6.
Nat Commun ; 14(1): 4457, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37491343

RESUMO

Topologically protected photonic edge states offer unprecedented robust propagation of photons that are promising for waveguiding, lasing, and quantum information processing. Here, we report on the discovery of a class of hybrid topological photonic crystals that host simultaneously quantum anomalous Hall and valley Hall phases in different photonic band gaps. The underlying hybrid topology manifests itself in the edge channels as the coexistence of the dual-band chiral edge states and unbalanced valley Hall edge states. We experimentally realize the hybrid topological photonic crystal, unveil its unique topological transitions, and verify its unconventional dual-band gap topological edge states using pump-probe techniques. Furthermore, we demonstrate that the dual-band photonic topological edge channels can serve as frequency-multiplexing devices that function as both beam splitters and combiners. Our study unveils hybrid topological insulators as an exotic topological state of photons as well as a promising route toward future applications in topological photonics.

7.
Opt Express ; 31(11): 17695-17708, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37381496

RESUMO

We systematically study the first- and second-order band topologies, which are tied to the pseudospin and valley degree of freedoms (DOFs), in honeycomb-kagome photonic crystals (HKPCs). We first demonstrate the quantum spin Hall phase as the first-order pseudospin-induced topology in HKPCs by observing the partial pseudospin-momentum locked edge states. By employing the topological crystalline index, we also discover the multiple corner states emerging in the hexagon-shaped supercell as the manifestation of the second-order pseudospin-induced topology in HKPCs. Next, by gapping the Dirac points, a lower band gap associated with the valley DOF emerges, in which the valley-momentum locked edge states are observed as the first-order valley-induced topology. Such HKPCs without inversion symmetry are proved to be Wannier-type second-order topological insulators, which manifested with valley-selective corner states. Additionally, we also discuss the symmetry breaking effect on pseudospin-momentum locked edge states. Our work realizes both pseudospin-induced and valley-induced topologies in a higher-order manner and thus provides more flexibility in manipulating electromagnetic waves, which may find potential applications in topological routings.

8.
Am J Cancer Res ; 13(2): 602-622, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36895988

RESUMO

Gastric cancer is one of the most common malignancies of the digestive system with high mortality rates. Recent studies have demonstrated that circRNAs are novel noncoding RNAs that play vital roles in the tumorigenesis and development of gastric cancer. Our study found a novel circRNA, namely, hsa_circ_0107595 (also called circABCA5), that is overexpressed in gastric cancer based on circRNA sequencing. qPCR demonstrated its overexpression in gastric cancer specimens. The overexpression or knockdown of circABCA5 in gastric cancer cell lines was achieved by lentiviral-mediated transfection. All MTS, EdU, Transwell and migration assays and xenograft experiments demonstrated that circABCA5 could promote gastric cancer proliferation, invasion, and migration in vitro and in vivo. Mechanistically, both RIP and RNA pulldown assays confirmed that circABCA5 could bind to the SPI1 protein, upregulate SPI1 expression, and promote its nuclear translocation. SPI1 could further promote the malignant phenotype of gastric cancer by activating IL6/JAK2/STAT3 signaling. In addition, EIF4A3 could directly bind to circABCA5, promoting its stability and expression. Our study reveals that circABCA5 plays a vital role in the diagnosis and prognosis of gastric cancer and may even be developed as a molecular target for the treatment of gastric cancer.

9.
Nat Genet ; 55(4): 665-678, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36959363

RESUMO

After severe heart injury, fibroblasts are activated and proliferate excessively to form scarring, leading to decreased cardiac function and eventually heart failure. It is unknown, however, whether cardiac fibroblasts are heterogeneous with respect to their degree of activation, proliferation and function during cardiac fibrosis. Here, using dual recombinase-mediated genetic lineage tracing, we find that endocardium-derived fibroblasts preferentially proliferate and expand in response to pressure overload. Fibroblast-specific proliferation tracing revealed highly regional expansion of activated fibroblasts after injury, whose pattern mirrors that of endocardium-derived fibroblast distribution in the heart. Specific ablation of endocardium-derived fibroblasts alleviates cardiac fibrosis and reduces the decline of heart function after pressure overload injury. Mechanistically, Wnt signaling promotes activation and expansion of endocardium-derived fibroblasts during cardiac remodeling. Our study identifies endocardium-derived fibroblasts as a key fibroblast subpopulation accounting for severe cardiac fibrosis after pressure overload injury and as a potential therapeutic target against cardiac fibrosis.


Assuntos
Cardiopatias , Fibroblastos/metabolismo , Cardiopatias/genética , Cardiopatias/patologia , Fibrose/genética , Animais , Camundongos , Envelhecimento , Proliferação de Células , Via de Sinalização Wnt , Camundongos Transgênicos
10.
Opt Express ; 30(10): 17204-17220, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-36221548

RESUMO

The simulation of fermionic relativistic physics, e.g., Dirac and Weyl physics, has led to the discovery of many unprecedented phenomena in photonics, of which the optical-frequency realization is, however, still challenging. Here, surprisingly, we discover that the woodpile photonic crystals commonly used for optical frequency applications host exotic fermion-like relativistic degeneracies: a Dirac nodal line and a fourfold quadratic point, as protected by the nonsymmorphic crystalline symmetry. Deforming the woodpile photonic crystal leads to the emergence of type-II Dirac points from the fourfold quadratic point. Such type-II Dirac points can be detected by its anomalous refraction property which is manifested as a giant birefringence in a slab setup. Our findings provide a promising route towards 3D optical Dirac physics in all-dielectric photonic crystals.

11.
J Biol Chem ; 298(6): 101965, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35461809

RESUMO

Genetic technology using site-specific recombinases, such as the Cre-loxP system, has been widely employed for labeling specific cell populations and for studying their functions in vivo. To enhance the precision of cell lineage tracing and functional study, a similar site-specific recombinase system termed Dre-rox has been recently used in combination with Cre-loxP. To enable more specific cell lineage tracing and ablation through dual recombinase activity, we generated two mouse lines that render Dre- or Dre+Cre-mediated recombination to excise a stop codon sequence that prevents the expression of diphtheria toxin receptor (DTR) knocked into the ubiquitously expressed and safe Rosa26 locus. Using different Dre- and Cre-expressing mouse lines, we showed that the surrogate gene reporters tdTomato and DTR were simultaneously expressed in target cells and in their descendants, and we observed efficient ablation of tdTomato+ cells after diphtheria toxin administration. These mouse lines were used to simultaneously trace and deplete the target cells of interest through the inducible expression of a reporter and DTR using dual Cre and Dre recombinases, allowing a more precise and efficient study of the role of specific cell subsets within a heterogeneous population in pathophysiological conditions in vivo.


Assuntos
Linhagem da Célula , Integrases , Recombinases , Animais , Integrases/genética , Integrases/metabolismo , Camundongos , Camundongos Transgênicos , Recombinases/genética , Recombinases/metabolismo , Recombinação Genética
12.
Opt Lett ; 47(6): 1454-1457, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35290337

RESUMO

The recent advancements in higher-order topology have provided unprecedented opportunities in optical device designs and applications. Here, we propose a new, to the best of our knowledge, method to realize rainbow trapping based on higher-order topological corner modes (HOTCMs), which are constructed by two configurations of breathing kagome photonic crystals with distinct topological phases. Interestingly, the HOTCMs localized at corners with different geometric configurations are found to be frequency dispersive and thus initiate the possible application in realizing rainbow trapping. By designing a polygon structure containing several configurations of corners, we demonstrate that the HOTCMs can be excited with the frequency sequence locked to the corner order (clockwise/anticlockwise direction) in the polygon. The reported HOTCMs provide a new mechanism to realize multiple-frequency trapping, which may find potential applications in future integrated photonics.

13.
J Mater Chem B ; 10(9): 1442-1452, 2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-35188167

RESUMO

Flexible strain sensors are attracting enormous attention due to their high stretchability and sensitivity that are required for wearable devices and electronic skin. However, diverse application environments require materials whose hardness can be adjusted to satisfy different demands. Herein, we developed a synergistic dual network hydrogel PANI-P(AAm-co-AA)@Fe3+ composed of an iron-coordinated poly(acrylamide-co-acrylic acid) network and a conductive polyaniline network with adjustable mechanical properties and high sensitivity. Through controlling the degree of protonation, the cross-linking density will be changed and the mechanical properties of PANI-P(AAm-co-AA)@Fe3+ can be regulated in a wide range (ultimate tensile stress: 0.0710-0.3054 MPa) (fracture strain: 145-880%). Besides, the host-guest interaction between ß-cyclodextrin (ß-CD) and polyaniline improves the compatibility of polyaniline in a hydrogel substance and leads to the formation of homogenous interpenetrating networks, which provide PANI-P(AAm-co-AA)@Fe3+ with outstanding and steady conductivity (2.03-3.67 S m-1). Furthermore, PANI-P(AAm-co-AA)@Fe3+ exhibits highly linear sensitivity, a wide working region (gauge factor = 0.48 at 0-400% strain) and excellent durability (300 cycles). A strain sensor based on this hydrogel can detect not only large movements such as bending fingers and wrists but also delicate movements such as swallowing and a pulse, indicating its enormous potential in wearable devices, human health monitoring, electronic skin, human-machine interactions and so on.


Assuntos
Hidrogéis , Dispositivos Eletrônicos Vestíveis , Condutividade Elétrica , Humanos
14.
Circ Res ; 130(3): 352-365, 2022 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-34995101

RESUMO

BACKGROUND: Unraveling how new coronary arteries develop may provide critical information for establishing novel therapeutic approaches to treating ischemic cardiac diseases. There are 2 distinct coronary vascular populations derived from different origins in the developing heart. Understanding the formation of coronary arteries may provide insights into new ways of promoting coronary artery formation after myocardial infarction. METHODS: To understand how intramyocardial coronary arteries are generated to connect these 2 coronary vascular populations, we combined genetic lineage tracing, light sheet microscopy, fluorescence micro-optical sectioning tomography, and tissue-specific gene knockout approaches to understand their cellular and molecular mechanisms. RESULTS: We show that a subset of intramyocardial coronary arteries form by angiogenic extension of endocardium-derived vascular tunnels in the neonatal heart. Three-dimensional whole-mount fluorescence imaging showed that these endocardium-derived vascular tunnels or tubes adopt an arterial fate in neonates. Mechanistically, we implicate Mettl3 (methyltransferase-like protein 3) and Notch signaling in regulating endocardium-derived intramyocardial coronary artery formation. Functionally, these intramyocardial arteries persist into adulthood and play a protective role after myocardial infarction. CONCLUSIONS: A subset of intramyocardial coronary arteries form by extension of endocardium-derived vascular tunnels in the neonatal heart.


Assuntos
Vasos Coronários/embriologia , Endocárdio/embriologia , Animais , Vasos Coronários/crescimento & desenvolvimento , Vasos Coronários/metabolismo , Endocárdio/crescimento & desenvolvimento , Endocárdio/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Organogênese
15.
Opt Express ; 29(24): 40606-40616, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809396

RESUMO

We proposed an one-dimensional layer-stacked photonic crystal using anisotropic materials to realize ideal type-II Weyl points. The topological transition from Dirac to Weyl points can be clearly observed by tuning the twist angle between layers. Also, on the interface between the photonic type-II Weyl material and air, gapless surface states have been demonstrated in an incomplete bulk bandgap. By breaking parameter symmetry, these ideal type-II Weyl points would transform into the non-ideal ones, exhibiting topological surface states with single group velocity. Our work may provide a new idea for the realization of photonic semimetal phases by utilizing naturally anisotropic materials.

16.
Cell Biosci ; 11(1): 177, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34583752

RESUMO

BACKGROUND: Although recent molecular analyses have improved our knowledge regarding gastric cancer (GC) biology, the molecular mechanisms that confer metastatic potential to GC remain poorly understood. In this study, we intend to explore the function and characterize the underlying mechanism of long noncoding RNA RNF144A-AS1 in GC metastasis and outgrowth. METHODS: The expression of RNF144A-AS1, miR-30c-2-3p, and Lysyl oxidase (LOX) was detected by quantitative real-time PCR assay. Fluorescence in situ hybridization and subcellular fractionation assay determined the cellular localization of RNF144A-AS1. Cell counting kit 8 assay, transwell assay, and tube formation assay were performed to detect the effect on cell proliferation, migration, invasion, and angiogenesis, respectively. Animal models were also applied to verify the effect on tumor metastasis, outgrowth, and angiogenesis. Bioinformatic analysis, luciferase reporter assay, and RNA immunoprecipitation (RIP) assay explored the interactions among RNF144A-AS1, miR-30c-2-3p, and LOX. Gene regulation was further validated by knockdown of Dicer or mutating the miRNA binding sites on RNF144A-AS1 and LOX 3'UTR. Cells were treated with recombinant human TGF-ß1 (Transforming Growth Factor ß1) to explore the effect of TGF-ß1 on RNF144A-AS1. Western blot and immunohistochemistry were used to detect protein expression. RESULTS: The expression of RNF144A-AS1 was significantly upregulated in GC tissues and was associated with poor prognosis and later-stage diseases. Hypoxia stimulated the expression of RNF144A-AS1 in a HIF-1α-independent manner. Additionally, RNF144A-AS1 was also induced by TGF-ß1. Loss and gain of function assays revealed that RNF144A-AS1 promoted tumor metastasis, angiogenesis, and proliferation. Mechanism exploration indicated RNF144A-AS1 served as a microRNA decoy of miR-30c-2-3p to release LOX. Gene Set Enrichment Analysis further suggested LOX and RNF144A-AS1 were enriched in the same gene sets, emphasizing the internal mechanism connection between these two genes. CONCLUSIONS: TGF-ß1- and hypoxia-inducible RNF144A-AS1 promoted tumor metastasis, angiogenesis, and proliferation through targeting the miR-30c-2-3p/LOX axis in GC, highlighting the value of the RNF144A-AS1/miR-30c-2-3p/LOX axis in therapeutic interventions of GC.

18.
Nat Commun ; 12(1): 2863, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001904

RESUMO

During injury, monocytes are recruited from the circulation to inflamed tissues and differentiate locally into mature macrophages, with prior reports showing that cavity macrophages of the peritoneum and pericardium invade deeply into the respective organs to promote repair. Here we report a dual recombinase-mediated genetic system designed to trace cavity macrophages in vivo by intersectional detection of two characteristic markers. Lineage tracing with this method shows accumulation of cavity macrophages during lung and liver injury on the surface of visceral organs without penetration into the parenchyma. Additional data suggest that these peritoneal or pleural cavity macrophages do not contribute to tissue repair and regeneration. Our in vivo genetic targeting approach thus provides a reliable method to identify and characterize cavity macrophages during their development and in tissue repair and regeneration, and distinguishes these cells from other lineages.


Assuntos
Fígado/fisiopatologia , Lesão Pulmonar/fisiopatologia , Macrófagos/fisiologia , Monócitos/fisiologia , Cavidade Peritoneal/fisiologia , Cavidade Pleural/fisiologia , Animais , Linhagem da Célula/genética , Células Cultivadas , Fígado/lesões , Ativação de Macrófagos/fisiologia , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Microscopia de Fluorescência/métodos , Monócitos/citologia , Monócitos/metabolismo , Cavidade Peritoneal/citologia , Fagocitose/fisiologia , Cavidade Pleural/citologia
19.
Nat Mater ; 20(6): 794-799, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33859382

RESUMO

Weyl semimetals (WSMs)1 exhibit phenomena such as Fermi arc surface states, pseudo-gauge fields and quantum anomalies that arise from topological band degeneracy in crystalline solids for electrons1 and metamaterials for photons2 and phonons3. Here we report a higher-order Weyl semimetal (HOWSM) in a phononic system that exhibits topologically protected boundary states in multiple dimensions. We created the physical realization of the HOWSM in a chiral phononic crystal with uniaxial screw symmetry. Using acoustic pump-probe spectroscopies, we observed coexisting chiral Fermi arc states on two-dimensional surfaces and dispersive hinge arc states on one-dimensional hinge boundaries. These topological boundary states link the projections of the Weyl points (WPs) in different dimensions and directions, and hence demonstrate the higher-order topological physics4-8 in WSMs. Our study further establishes the fundamental connection between higher-order topology and Weyl physics in crystalline materials and should stimulate further work on other potential materials, such as higher-order topological nodal-line semimetals.

20.
J Exp Clin Cancer Res ; 40(1): 6, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33397440

RESUMO

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors worldwide. Currently, the overall survival rate of GC is still unsatisfactory despite progress in diagnosis and treatment. Therefore, studying the molecular mechanisms involved in GC is vital for diagnosis and treatment. CircRNAs, a type of noncoding RNA, have been proven to act as miRNA sponges that can widely regulate various cancers. By this mechanism, circRNA can regulate tumors at the genetic level by releasing miRNA from inhibiting its target genes. The WNT2/ß-Catenin regulatory pathway is one of the canonical signaling pathways in tumors. It can not only promote the development of tumors but also provide energy for tumor growth through cell metabolism (such as glutamine metabolism). METHODS: Through RNA sequencing, we found that hsa_circ_0008259 (circLMO7) was highly expressed in GC tissues. After verifying the circular characteristics of circLMO7, we determined the downstream miRNA (miR-30a-3p) of circLMO7 by RNA pull-down and luciferase reporter assays. We verified the effect of circLMO7 and miR-30a-3p on GC cells through a series of functional experiments, including colony formation, 5-ethynyl-2'-deoxyuridine and Transwell assays. Through Western blot and immunofluorescence analyses, we found that WNT2 was the downstream target gene of miR-30a-3p and further confirmed that the circLMO7-miR-30a-3p-WNT2 axis could promote the development of GC. In addition, measurement of related metabolites confirmed that this axis could also provide energy for the growth of GC cells through glutamine metabolism. We found that circLMO7 could promote the growth and metastasis of GC in vivo by the establishment of nude mouse models. Finally, we also demonstrated that HNRNPL could bind to the flanking introns of the circLMO7 exons to promote circLMO7 cyclization. RESULTS: CircLMO7 acted as a miR-30a-3p sponge affecting the WNT2/ß-Catenin pathway to promote the proliferation, migration and invasion of GC cells. Moreover, animal results also showed that circLMO7 could promote GC growth and metastasis in vivo. CircLMO7 could also affect the glutamine metabolism of GC cells through the WNT2/ß-Catenin pathway to promote its malignant biological function. In addition, we proved that HNRNPL could promote the self-cyclization of circLMO7. CONCLUSIONS: CircLMO7 promotes the development of GC by releasing the inhibitory effect of miR-30a-3p on its target gene WNT2.


Assuntos
RNA Circular/metabolismo , Neoplasias Gástricas/genética , Proteína Wnt2/metabolismo , beta Catenina/metabolismo , Animais , Progressão da Doença , Humanos , Camundongos , MicroRNAs , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida
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