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1.
Angew Chem Int Ed Engl ; : e202402946, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38696279

ABSTRACT

Electrolytes with anion-dominated solvation are promising candidates to achieve dendrite-free and high-voltage potassium metal batteries. However, it's challenging to form anion-reinforced solvates at low salt concentrations. Herein, we construct an anion-reinforced solvation structure at a moderate concentration of 1.5 M with weakly coordinated cosolvent ethylene glycol dibutyl ether. The unique solvation structure accelerates the desolvation of K+, strengthens the oxidative stability to 4.94 V and facilitates the formation of inorganic-rich and stable electrode-electrolyte interface. These enable stable plating/stripping of K metal anode over 2200 h, high capacity retention of 83.0% after 150 cycles with a high cut-off voltage of 4.5 V in K0.67MnO2//K cells, and even 91.5% after 30 cycles under 4.7 V. This work provides insight into weakly coordinated cosolvent and opens new avenues for designing ether-based high-voltage electrolytes.

2.
Chem Sci ; 15(19): 7144-7149, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38756800

ABSTRACT

Garnet-type solid-state Li metal batteries (SSLMBs) are viewed as hopeful next-generation batteries due to their high energy density and safety. However, the major obstacle to the development of garnet-type SSLMBs is the lithiophobicity of Li6.75La3Zr1.75Ta0.25O12 (LLZTO), resulting in a large interfacial impedance. Herein, a LiI/ZnLix mixed ion/electron conductive buffer layer is constructed at the interface by an in situ reaction of molten Li metal with ZnI2 film. This mixed buffer layer ensures close contact between the Li metal and garnet, significantly reducing interfacial impedance. As a result, the Li symmetrical cell with the LiI/ZnLix buffer layer shows an interface impedance of 10.3 Ω cm2, much lower than that of the cell with bare LLZTO (1173.4 Ω cm2). The critical current density (CCD) is up to 2.3 mA cm-2, and the symmetric cells present a long cycle life of 2000 h at 0.1 mA cm-2 and 800 h at 1.0 mA cm-2. In addition, the full cells assembled with the LiFePO4 cathode show a capacity of 143.9 mA h g-1 after 200 cycles at 0.5C with a low-capacity decay of 0.021% per cycle. This work reveals a simple, feasible, and practical interface modification strategy for solid-state Li metal batteries.

3.
Adv Mater ; : e2400169, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38607696

ABSTRACT

Intrinsically safe sodium-ion batteries are considered as a promising candidate for large-scale energy storage systems. However, the high flammability of conventional electrolytes may pose serious safety threats and even explosions. Herein, a strategy of constructing a deep eutectic electrolyte is proposed to boost the safety and electrochemical performance of succinonitrile (SN)-based electrolyte. The strong hydrogen bond between S═O of 1,3,2-dioxathiolane-2,2-dioxide (DTD) and the α-H of SN endows the enhanced safety and compatibility of SN with Lewis bases. Meanwhile, the DTD participates in the inner Na+ sheath and weakens the coordination number of SN. The unique solvation configuration promotes the formation of robust gradient inorganic-rich electrode-electrolyte interphase, and merits stable cycling of half-cells in a wide temperature range, with a capacity retention of 82.8% after 800 cycles (25 °C) and 86.3% after 100 cycles (60 °C). Correspondingly, the full cells deliver tremendous improvement in cycling stability and rate performance.

4.
Chem Sci ; 15(13): 4833-4838, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38550702

ABSTRACT

Sodium metal batteries have attracted increasing interest recently, but suffer from severe dendrite growth caused by uneven Na plating/stripping behavior, which may result in the piercing of the membrane, with short circuiting and even cause explosions. Herein, a conductive and sodiophilic Ag coating layer is introduced to regulate Na deposition behaviors for highly reversible sodium metal batteries. Ag coated Zn foil with enhanced sodiophilicity, rapid Na+ transfer kinetics and superior electronic conductivity guarantee the homogenized Na+ ion and electric field distribution. This enables remarkably low overpotentials and uniform Na plating/stripping behavior with ultrahigh Coulombic efficiency of 99.9% during 500 cycles. As expected, the enhanced electrochemical performance of the anode-less battery and anode-free battery coupled with Prussian blue is achieved with the help of Ag coating. This work emphasizes the role of the conductive and sodiophilic coating layer in regulating the Na deposition behaviors for highly reversible sodium metal batteries.

5.
ACS Nano ; 18(13): 9354-9364, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38517038

ABSTRACT

Na3V2(PO4)3 (NVP) based on the multielectron reactions between V2+ and V5+ has been considered a promising cathode for sodium-ion batteries (SIBs). However, it still suffers from unsatisfactory stability, caused by the poor reversibility of the V5+/V4+ redox couple and structure evolution. Herein, we propos a strategy that combines high-entropy substitution and electrolyte optimization to boost the reversible multielectron reactions of NVP. The high reversibility of the V5+/V4+ redox couple and crystalline structure evolution are disclosed by in situ X-ray absorption near-edge structure spectra and in situ X-ray diffraction. Meanwhile, the electrochemical reaction kinetics of high-entropy substitution NVP (HE-NVP) can be further improved in the diglyme-based electrolyte. These enable HE-NVP to deliver a superior electrochemical performance (capacity retention of 93.1% after 2000 cycles; a large reversible capacity of 120 mAh g-1 even at 5.0 A g-1). Besides, the long cycle life and high power density of the HE-NVP∥natural graphite full-cell configuration demonstrated the superiority of HE-NVP cathode in SIBs. This work highlights that the synergism of high-entropy substitution and electrolyte optimization is a powerful strategy to enhance the sodium-storage performance of polyanionic cathodes for SIBs.

6.
Angew Chem Int Ed Engl ; 63(21): e202402342, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38491787

ABSTRACT

Zn deposition with a surface-preferred (002) crystal plane has attracted extensive attention due to its inhibited dendrite growth and side reactions. However, the nucleation and growth of the Zn(002) crystal plane are closely related to the interfacial properties. Herein, oriented growth of Zn(002) crystal plane is realized on Ag-modified surface that is directly visualized by in situ atomic force microscopy. A solid solution HCP-Zn (~1.10 at. % solubility of Ag, 30 °C) is formed on the Ag coated Zn foil (Zn@Ag) and possesses the same crystal structure as Zn to reduce its nucleation barrier caused by their lattice mismatch. It merits oriented Zn deposition and corrosion-resistant surface, and presents long cycling stability in symmetric cells and full cells coupled with V2O5 cathode. This work provides insights into interfacial regulation of Zn anodes for high-performance aqueous zinc metal batteries.

7.
Angew Chem Int Ed Engl ; 63(21): e202400406, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38491786

ABSTRACT

Diluents have been extensively employed to overcome the disadvantages of high viscosity and sluggish kinetics of high-concentration electrolytes, but generally do not change the pristine solvation structure. Herein, a weakly coordinating diluent, hexafluoroisopropyl methyl ether (HFME), is applied to regulate the coordination of Na+ with diglyme and anion and form a diluent-participated solvate. This unique solvation structure promotes the accelerated decomposition of anions and diluents, with the construction of robust inorganic-rich electrode-electrolyte interphases. In addition, the introduction of HFME reduces the desolvation energy of Na+, improves ionic conductivity, strengthens the antioxidant, and enhances the safety of the electrolyte. As a result, the assembled Na||Na symmetric cell achieves a stable cycle of over 1800 h. The cell of Na||P'2-Na0.67MnO2 delivers a high capacity retention of 87.3 % with a high average Coulombic efficiency of 99.7 % after 350 cycles. This work provides valuable insights into solvation chemistry for advanced electrolyte engineering.

8.
Chem Sci ; 15(11): 4135-4139, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38487247

ABSTRACT

Na2Fe2(SO4)3 (NFS), as a promising cathode for sodium-ion batteries, is still plagued by its poor intrinsic conductivity. In general, hybridization with carbon materials is an effective strategy to improve the sodium storage performance of NFS. However, the role of carbon materials in the electrochemical performance of NFS cathode materials has not been thoroughly investigated. Herein, the effect of carbon materials was revealed by employing various conductive carbon materials as carbon sources. Among these, the NFS coated with Ketjen Black (NFS@KB) shows the largest specific surface area, which is beneficial for electrolyte penetration and rapid ionic/electronic migration, leading to improved electrochemical performance. Therefore, NFS@KB shows a long cycle life (74.6 mA h g-1 after 1000 cycles), superior rate performance (61.5 mA h g-1 at a 5.0 A g-1), and good temperature tolerance (-10 °C to 60 °C). Besides, the practicality of the NFS@KB cathode was further demonstrated by assembling a NFS@KB//hard carbon full cell. Therefore, this research indicates that a suitable carbon material for the NFS cathode can greatly activate the sodium storage performance.

9.
Proc Natl Acad Sci U S A ; 121(5): e2316914121, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38252828

ABSTRACT

High-performance sodium storage at low temperature is urgent with the increasingly stringent demand for energy storage systems. However, the aggravated capacity loss is induced by the sluggish interfacial kinetics, which originates from the interfacial Na+ desolvation. Herein, all-fluorinated anions with ultrahigh electron donicity, trifluoroacetate (TFA-), are introduced into the diglyme (G2)-based electrolyte for the anion-reinforced solvates in a wide temperature range. The unique solvation structure with TFA- anions and decreased G2 molecules occupying the inner sheath accelerates desolvation of Na+ to exhibit decreased desolvation energy from 4.16 to 3.49 kJ mol-1 and 24.74 to 16.55 kJ mol-1 beyond and below -20 °C, respectively, compared with that in 1.0 M NaPF6-G2. These enable the cell of Na||Na3V2(PO4)3 to deliver 60.2% of its room-temperature capacity and high capacity retention of 99.2% after 100 cycles at -40 °C. This work highlights regulation of solvation chemistry for highly stable sodium-ion batteries at low temperature.

10.
Adv Mater ; 36(7): e2305135, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37590909

ABSTRACT

Sodium-ion batteries (SIBs) are a viable alternative to meet the requirements of future large-scale energy storage systems due to the uniform distribution and abundant sodium resources. Among the various cathode materials for SIBs, phosphate-based polyanionic compounds exhibit excellent sodium-storage properties, such as high operation voltage, remarkable structural stability, and superior safety. However, their undesirable electronic conductivities and specific capacities limit their application in large-scale energy storage systems. Herein, the development history and recent progress of phosphate-based polyanionic cathodes are first overviewed. Subsequently, the effective modification strategies of phosphate-based polyanionic cathodes are summarized toward high-performance SIBs, including surface coating, morphological control, ion doping, and electrolyte optimization. Besides, the electrochemical performance, cost, and industrialization analysis of phosphate-based polyanionic cathodes for SIBs are discussed for accelerating commercialization development. Finally, the future directions of phosphate-based polyanionic cathodes are comprehensively concluded. It is believed that this review can provide instructive insight into developing practical phosphate-based polyanionic cathodes for SIBs.

11.
Angew Chem Int Ed Engl ; 63(3): e202313142, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-37917045

ABSTRACT

Sodium dual-ion batteries (Na-DIBs) have attracted increasing attention due to their high operative voltages and low-cost raw materials. However, the practical applications of Na-DIBs are still hindered by the issues, such as low capacity and poor Coulombic efficiency, which is highly correlated with the compatibility between electrode and electrolyte but rarely investigated. Herein, fluoroethylene carbonate (FEC) is introduced into the electrolyte to regulate cation/anion solvation structure and the stability of cathode/anode-electrolyte interphase of Na-DIBs. The FEC modulates the environment of PF6 - solvation sheath and facilitates the interaction of PF6 - on graphite. In addition, the NaF-rich interphase caused by the preferential decomposition of FEC effectively inhibits side reactions and pulverization of anodes with the electrolyte. Consequently, Sb||graphite full cells in FEC-containing electrolyte achieve an improved capacity, cycling stability and Coulombic efficiency. This work elucidates the underlying mechanism of bifunctional FEC and provides an alternative strategy of building high-performance dual ion batteries.

12.
Angew Chem Int Ed Engl ; 62(39): e202308888, 2023 Sep 25.
Article in English | MEDLINE | ID: mdl-37530650

ABSTRACT

High-voltage lithium-ion batteries (LIBs) have attracted great attention due to their promising high energy density. However, severe capacity degradation is witnessed, which originated from the incompatible and unstable electrolyte-electrode interphase at high voltage. Herein, a robust additive-induced sulfur-rich interphase is constructed by introducing an additive with ultrahigh S-content (34.04 %, methylene methyl disulfonate, MMDS) in 4.6 V LiNi0.5 Co0.2 Mn0.3 O2 (NCM523)||graphite pouch cell. The MMDS does not directly participate the inner Li+ sheath, but the strong interactions between MMDS and PF6 - anions promote the preferential decomposition of MMDS and broaden the oxidation stability, facilitating the formation of an ultrathin but robust sulfur-rich interfacial layer. The electrolyte consumption, gas production, phase transformation and dissolution of transition metal ions were effectively inhibited. As expected, the 4.6 V NCM523||graphite pouch cell delivers a high capacity retention of 87.99 % even after 800 cycles. This work shares new insight into the sulfur-rich additive-induced electrolyte-electrode interphase for stable high-voltage LIBs.

13.
Adv Mater ; 35(17): e2210082, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36738238

ABSTRACT

Sustainable organic electrode materials, as promising alternatives to conventional inorganic electrode materials for sodium-ion batteries (SIBs), are still challenging to realize long-lifetime and high-rate batteries because of their poor conductivity, limited electroactivity, and severe dissolution. It is also urgent to deeply reveal their electrochemical mechanism and evolution processes. A porous organic polymer (POP) with a conjugated and hierarchical structure is designed and synthesized here. The unique molecule and structure endow the POP with electron delocalization, high ionic diffusivity, plentiful active sites, exceptional structure stability, and limited solubility in electrolytes. When evaluated as an anode for SIBs, the POP exhibits appealing electrochemical properties regarding reversible capacity, rate behaviors, and long-duration life. Importantly, using judiciously combined experiments and theoretical computation, including in situ transmission electron microscopy (TEM), and ex situ spectroscopy, we reveal the Na-storage mechanism and dynamic evolution processes of the POP, including 12-electron reaction process with Na, low volume expansion (125-106% vs the initial 100%), and stable composition and structure evolution during repeating sodiation/de-sodiation processes. This quantitative design for ultrafast and highly durable sodium storage in the POP could be of immediate benefit for the rational design of organic electrode materials with ideal electrochemical properties.

14.
J Am Chem Soc ; 144(25): 11129-11137, 2022 06 29.
Article in English | MEDLINE | ID: mdl-35700394

ABSTRACT

The hydrophobic internal cavity and hydrophilic external surface of cyclodextrins (CDs) render promising electrochemical applications. Here, we report a comparative and mechanistic study on the use of CD molecules (α-, ß-, and γ-CD) as electrolyte additives for rechargeable Zn batteries. The addition of α-CD in aqueous ZnSO4 solution reduces nucleation overpotential and activation energy of Zn plating and suppresses H2 generation. Computational, spectroscopic, and electrochemical studies reveal that α-CD preferentially adsorbs in parallel on the Zn surface via secondary hydroxyl groups, suppressing water-induced side reactions of hydrogen evolution and hydroxide sulfate formation. Additionally, the hydrophilic exterior surface of α-CD with intense electron density simultaneously facilitates Zn2+ deposition and alleviates Zn dendrite formation. A formulated 3 M ZnSO4 + 10 mM α-CD electrolyte enables homogenous Zn plating/stripping (average Coulombic efficiency ∼ 99.90%) at 1 mA cm-2 in Zn|Cu cells and a considerable capacity retention of 84.20% after 800 cycles in Zn|V2O5 full batteries. This study provides insight into the use of supramolecular macrocycles to modulate and enhance the interface stability and kinetics of metallic anodes for aqueous battery chemistry.


Subject(s)
Cyclodextrins , Cyclodextrins/chemistry , Electrodes , Kinetics , Water , Zinc
15.
Angew Chem Int Ed Engl ; 61(30): e202205045, 2022 Jul 25.
Article in English | MEDLINE | ID: mdl-35533111

ABSTRACT

Metallic Na is a promising anode for rechargeable batteries, however, it is plagued by an unstable solid electrolyte interphase (SEI) and Na dendrites. Herein, a robust anion-derived SEI is constructed on Na anode in a high-concentration 1,2-dimethoxyethane (DME) based electrolyte with a cosolvent hydrofluoroether, which effectively restrains Na dendrite growth. The hydrofluoroether can tune the solvation configuration of the electrolyte from three-dimensional network aggregates to solvent-cation-anion clusters, enabling more anions to enter and reinforce the inner solvation sheath and their stepwise decomposition. The gradient inorganic-rich SEI leads to a reduced energy barrier of Na+ migration and enhanced interfacial kinetics. These render the Na||Na3 V2 (PO4 )3 battery with an excellent rate capability of 79.9 mAh g-1 at 24 C and a high capacity retention of 94.2 % after 6000 cycles at 2 C. This highlights the modulation of the electrode-electrolyte interphase chemistry for advanced batteries.

16.
ACS Appl Mater Interfaces ; 13(44): 53227-53234, 2021 Nov 10.
Article in English | MEDLINE | ID: mdl-34699184

ABSTRACT

Zn anodes have gained intensive attention for their environmental-friendliness and high volumetric capacity but are limited by their severe dendrite formation. Understanding the initial nucleation behavior is critical for manipulating the uniform deposition of Zn. Herein, the allometric growth and dissolution of Zn in the initial nucleation and early stages are visualized with in situ atomic force microscopy in aqueous ZnCl2 electrolytes. Zn nuclei grow via a horizontal radial direction and dissolve reversibly in a top-down process. The critical nucleation radius and density are dependent on the electrolyte concentration of ZnCl2, namely, the initial nucleus size is proportional to the ratio of surface free energy between deposited Zn and the electrolyte and overpotentials for Zn electrodeposition, and the density is inversely proportional to the cube of this ratio. This investigation provides guidelines for regulating uniform metal electrodeposition and yields benefits for the development of anode-free batteries.

17.
Angew Chem Int Ed Engl ; 60(43): 23357-23364, 2021 Oct 18.
Article in English | MEDLINE | ID: mdl-34382322

ABSTRACT

Rechargeable aqueous Zn batteries are potential for large-scale electrochemical energy storage due to their low cost and high security. However, Zn metal anode suffers from the dendritic growth and interfacial hydrogen evolution reaction (HER), resulting in the deterioration of electrode/battery performance. Here we propose that both dendrites and HER are related to the water participated Zn2+ solvation structure-Zn(H2 O)6 2+ and thus can be resolved by transforming Zn(H2 O)6 2+ to an anion-type water-free solvation structure-ZnCl4 2- , which is achieved in traditional ZnSO4 aqueous electrolyte after adding chloride salt with a bulky cation (1-ethyl-3-methylimidazolium chloride). The elimination of cation-water interaction suppresses HER, while the electrostatic repulsion between Zn tips and the anion solvation structure inhibits dendrite formation. As a result, the electrolyte shows uniform Zn deposition with an average Zn plating/stripping Coulombic efficiency of ≈99.9 %, enabling a capacity retention of 78.8 % after 300 cycles in anode-free Zn batteries with pre-zincificated polyaniline as the cathode. This work provides a novel electrolyte design strategy to prevent HER and realize long-lifespan metal anode.

18.
Cell Death Dis ; 12(3): 275, 2021 03 15.
Article in English | MEDLINE | ID: mdl-33723215

ABSTRACT

Ovarian cancer (OC) causes more deaths than any other gynecological cancer. Many cellular pathways have been elucidated to be associated with OC development and progression. Specifically, the insulin-like growth factor 1 receptor/insulin receptor substrate 1 (IGF1R/IRS1) pathway participates in OC development. Moreover, accumulating evidence has shown that microRNA deregulation contributes to tumor initiation and progression. Here, our study aimed to investigate the molecular functions and regulatory mechanisms of miR-150, specifically, in OC. We found that the expression of miR-150-5p/3p and their precursor, mir-150, was downregulated in OC tissues; lower mir-150 levels were associated with poor OC patient outcomes. Ectopic mir-150 expression inhibited OC cell growth and metastasis in vitro and in vivo. Furthermore, both IRS1 and IGF1R were confirmed as direct targets of miR-150-5p/3p, and the miR-150-IGF1R/IRS1 axis exerted antitumor effects via the PI3K/AKT/mTOR pathway. Forkhead box protein 3 (FoxP3) positively regulated the expression of miR-150-5p/3p by binding to the mir-150 promoter. In turn, the PI3K/AKT/mTOR pathway downregulated FoxP3 and miR-150-5p/3p. Taken together, these findings indicate that a complex FoxP3-miR-150-IGF1R/IRS1-PI3K/AKT/mTOR feedback loop regulates OC pathogenesis, providing a novel mechanism for miR-150 as a tumor suppressor miRNA in OC.


Subject(s)
Cell Movement , Cell Proliferation , Forkhead Transcription Factors/metabolism , Insulin Receptor Substrate Proteins/metabolism , MicroRNAs/metabolism , Ovarian Neoplasms/metabolism , Receptor, IGF Type 1/metabolism , Animals , Apoptosis , Cell Line, Tumor , Feedback, Physiological , Female , Forkhead Transcription Factors/genetics , Gene Expression Regulation, Neoplastic , HEK293 Cells , Humans , Insulin Receptor Substrate Proteins/genetics , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/genetics , Neoplasm Invasiveness , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Phosphatidylinositol 3-Kinase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Receptor, IGF Type 1/genetics , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Tumor Burden
19.
ACS Appl Mater Interfaces ; 12(49): 55476-55482, 2020 Dec 09.
Article in English | MEDLINE | ID: mdl-33237733

ABSTRACT

Direct monitoring of dendrite growth, hydrogen evolution, and surface passivation can enrich the chemical and morphological understanding of the unstable Zn/electrolyte interface and provide guidelines for rational design of Zn anodes; however, the on-line observation with high precision is hitherto lacking. Herein, we present a real-time comprehensive characterization system, including in situ atomic force microscopy, optical microscopy, and electrochemical quartz crystal microbalance (referred to as the "3M" system), to provide multiscale views on the semisphere nuclei and growth of bump-like dendrites and the potential-dependent chemical and morphological structures of passivated products in a mild acidic electrolyte. It is revealed that the poor interfacial properties can be attributed to the sparse nucleation sites and direct contact of Zn with the electrolyte. The 3M system further visualizes and confirms that the additive polyethylene glycol acts as a Zn2+ distribution promoter and physical barrier and merits stable electrochemical performance.

20.
J Exp Clin Cancer Res ; 38(1): 249, 2019 Jun 11.
Article in English | MEDLINE | ID: mdl-31186036

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is the third most frequent cancer and the second leading cause of cancer-related death worldwide. Increasing evidence indicates that the deregulation of long noncoding RNAs (lncRNAs) contributes to tumor initiation and progression; however, little is known about the biological role of cancer susceptibility candidate 9 (CASC9) in CRC. METHODS: Novel lncRNAs potentially involved in CRC tumorigenesis were identified from datasets downloaded from The Cancer LncRNome Atlas and The Atlas of Noncoding RNAs in Cancer. The CRC cell lines HCT-116, HCT-116 p53-/-, SW620, SW480, HT-29, LoVo, LS-174T, and RKO were used. Colony-formation, MTS, cell-cycle, apoptosis, and in-vivo tumorigenesis assays were used to determine the role of CASC9 in CRC cell growth in vitro and in vivo. Potential interaction between CASC9 and cleavage and polyadenylation specificity factor subunit 3 (CPSF3) was evaluated using RNA immunoprecipitation and RNA-protein pull-down assays. RNA-sequencing was performed to analyze gene expression following CASC9 knockdown. RT-qPCR, western blotting, and mRNA decay assays were performed to study the mechanisms involved. RESULTS: CASC9 was frequently upregulated in CRC, which was correlated with advanced TNM stage, and higher CASC9 levels were associated with poor patient outcomes. Knockdown of CASC9 inhibited growth and promoted apoptosis in CRC cells, whereas ectopic CASC9 expression promoted cell growth in vitro and in vivo. We demonstrated that CPSF3 is a CASC9-interacting protein, and knockdown of CPSF3 mimicked the effects of CASC9 knockdown in CRC cells. Furthermore, we found that CASC9 exerts its oncogenic activity by modulating TGFß2 mRNA stability and upregulating the levels of TGFß2 and TERT, resulting in an increase in phosphorylated SMAD3 and activation of TGF-ß signaling, and enhanced TERT complex function in CRC cells. Finally, CPSF3 was significantly upregulated in CRC tissues as compared with adjacent or non-adjacent normal colon tissues, and CASC9, CPSF3, and TGFß2 levels in human CRC tissues were positively correlated. CONCLUSIONS: CASC9 is a promising prognostic predictor for patients with CRC and the CASC9-CPSF3-TGFß2 axis is a potential therapeutic target for CRC treatment.


Subject(s)
Cleavage And Polyadenylation Specificity Factor/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , RNA, Long Noncoding/genetics , Signal Transduction , Transforming Growth Factor beta/metabolism , Aged , Aged, 80 and over , Apoptosis/genetics , Biomarkers, Tumor , Cell Cycle/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation , Colorectal Neoplasms/pathology , Female , Gene Expression Regulation, Neoplastic , Heterografts , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Metastasis , Neoplasm Staging , RNA Interference , Tumor Burden
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