KCNK1 promotes proliferation and metastasis of breast cancer cells by activating lactate dehydrogenase A (LDHA) and up-regulating H3K18 lactylation.

Breast cancer is the most prevalent malignancy and the most significant contributor to mortality in female oncology patients. Potassium Two Pore Domain Channel Subfamily K Member 1 (KCNK1) is differentially expressed in a variety of tumors, but the mechanism of its function in breast cancer is unknown. In this study, we found for the first time that KCNK1 was significantly up-regulated in human breast cancer and was correlated with poor prognosis in breast cancer patients. KCNK1 promoted breast cancer proliferation, invasion, and metastasis in vitro and vivo. Further studies unexpectedly revealed that KCNK1 increased the glycolysis and lactate production in breast cancer cells by binding to and activating lactate dehydrogenase A (LDHA), which promoted histones lysine lactylation to induce the expression of a series of downstream genes and LDHA itself. Notably, increased expression of LDHA served as a vicious positive feedback to reduce tumor cell stiffness and adhesion, which eventually resulted in the proliferation, invasion, and metastasis of breast cancer. In conclusion, our results suggest that KCNK1 may serve as a potential breast cancer biomarker, and deeper insight into the cancer-promoting mechanism of KCNK1 may uncover a novel therapeutic target for breast cancer treatment.

COP1 positively regulates ABA signaling during Arabidopsis seedling growth in darkness by mediating ABA-induced ABI5 accumulation.

CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1), a well-characterized E3 ubiquitin ligase, is a central repressor of seedling photomorphogenic development in darkness. However, whether COP1 is involved in modulating abscisic acid (ABA) signaling in darkness remains largely obscure. Here, we report that COP1 is a positive regulator of ABA signaling during Arabidopsis seedling growth in the dark. COP1 mediates ABA-induced accumulation of ABI5, a transcription factor playing a key role in ABA signaling, through transcriptional and post-translational regulatory mechanisms. We further show that COP1 physically interacts with ABA-hypersensitive DCAF1 (ABD1), a substrate receptor of the CUL4-DDB1 E3 ligase targeting ABI5 for degradation. Accordingly, COP1 directly ubiquitinates ABD1 in vitro, and negatively regulates ABD1 protein abundance in vivo in the dark but not in the light. Therefore, COP1 promotes ABI5 protein stability post-translationally in darkness by destabilizing ABD1 in response to ABA. Interestingly, we reveal that ABA induces the nuclear accumulation of COP1 in darkness, thus enhancing its activity in propagating the ABA signal. Together, our study uncovers that COP1 modulates ABA signaling during seedling growth in darkness by mediating ABA-induced ABI5 accumulation, demonstrating that plants adjust their ABA signaling mechanisms according to their light environment.

In Situ Growth of Sodium Manganese Hexacyanoferrate on Carbon Nanotubes for High-Performance Sodium-Ion Batteries.

Sodium manganese hexacyanoferrate (NaMnHCF) has emerged as a research hotspot among Prussian blue analogs for sodium-ion battery cathode materials due to its advantages of high voltage, high specific capacity, and abundant raw materials. However, its practical application is limited by its poor electronic conductivity. In this study, we aim to solve this problem through the in situ growth of NaMnHCF on carbon nanotubes (CNTs) using a simple coprecipitation method. The results show that the overall electronic conductivity of NaMnHCF is significantly improved after the introduction of CNTs. The NaMnHCF@10%CNT sample presents a specific capacity of 90 mA h g-1, even at a current density of 20 C (2400 mA g-1). The study shows that the optimized composite exhibits a superior electrochemical performance at different mass loadings (from low to high), which is attributed to the enhanced electron transport and shortened electron pathway. Surprisingly, the cycling performance of the composites was also improved, resulting from decreased polarization and the subsequent reduction in the side reactions at the cathode/electrolyte interface. Furthermore, we revealed the evolution of potential plateau roots from the extraction of crystal water during the charge-discharge process of NaMnHCF based on the experimental results. This study is instructive not only for the practical application of NaMnHCF materials but also for advancing our scientific understanding of the behavior of crystal water during the charge-discharge process.

Hydrazone-Linked Covalent Organic Frameworks.

Hydrazone-linked covalent organic frameworks (COFs) with structural flexibility, heteroatomic sites, post-modification ability and high hydrolytic stability have attracted great attention from scientific community. Hydrazone-linked COFs, as a subclass of Schiff-base COFs, was firstly reported in 2011 by Yaghi's group and later witnessed prosperous development in various aspects. Their adjustable structures, precise pore channels and plentiful heteroatomic sites of hydrazone-linked structures possess much potential in diverse applications, for example, adsorption/separation, chemical sensing, catalysis and energy storage, etc. Up to date, the systematic reviews about the reported hydrazone-linked COFs are still rare. Therefore, in this review, we will summarize their preparation methods, characteristics and related applications, and discuss the opportunity or challenge of hydrazone-linked COFs. We hope this review could provide new insights about hydrazone-linked COFs for exploring more appealing functions or applications.

Zigzag Hopping Site Embedded Covalent Organic Frameworks Coating for Zn Anode.

Precise design and tuning of Zn hopping/transfer sites with deeper understanding of the dendrite-formation mechanism is vital in artificial anode protective coating for aqueous Zn-ion batteries (AZIBs). Here, we probe into the role of anode-coating interfaces by designing a series of anhydride-based covalent organic frameworks (i.e., PI-DP-COF and PI-DT-COF) with specifically designed zigzag hopping sites and zincophilic anhydride groups that can serve as desired platforms to investigate the related Zn2+ hopping/transfer behaviours as well as the interfacial interaction. Combining theoretical calculations with experiments, the ABC stacking models of these COFs endow the structures with specific zigzag sites along the 1D channel that can accelerate Zn2+ transfer kinetics, lower surface-energy, homogenize ion-distribution or electric-filed. Attributed to these superiorities, thus-obtained optimal PI-DT-COF cells offer excellent cycling lifespan in both symmetric-cell (2000 cycles at 60 mA cm-2) and full-cell (1600 cycles at 2 A g-1), outperforming almost all the reported porous crystalline materials.

Redox Molecular Junction Metal-Covalent Organic Frameworks for Light-assisted CO2 Energy Storage.

Visible-light sensitive and bi-functionally favored CO2 reduction (CRR)/evolution (CER) photocathode catalysts that can get rid of the utilization of ultraviolet light and improve sluggish kinetics is demanded to conquer the current technique-barrier of traditional Li-CO2 battery. Here, a kind of redox molecular junction sp2c metal-covalent organic framework (i.e. Cu3-BTDE-COF) has been prepared through the connection between Cu3 and BTDE and can serve as efficient photocathode catalyst in light-assisted Li-CO2 battery. Cu3-BTDE-COF with redox-ability, visible-light-adsorption region, electron-hole separation ability and endows the photocathode with excellent round-trip efficiency (95.2 %) and an ultralow voltage hysteresis (0.18 V), outperforming the Schiff base COFs (i.e. Cu3-BTDA-COF and Cu3-DT-COF) and majority of the reported photocathode catalysts. Combined theoretical calculations with characterizations, Cu3-BTDE-COF with the integration of Cu3 centers, thiazole and cyano groups possess strong CO2 adsorption/activation and Li+ interaction/diffusion ability to boost the CRR/CER kinetics and related battery property.

Modulated Connection Modes of Redox Units in Molecular Junction Covalent Organic Frameworks for Artificial Photosynthetic Overall Reaction.

The precise tuning of components, spatial orientations, or connection modes for redox units is vital for gaining deep insight into efficient artificial photosynthetic overall reaction, yet it is still hard achieve for heterojunction photocatalysts. Here, we have developed a series of redox molecular junction covalent organic frameworks (COFs) (M-TTCOF-Zn, M = Bi, Tri, and Tetra) for artificial photosynthetic overall reaction. The covalent connection between TAPP-Zn and multidentate TTF endows various connection modes between water photo-oxidation (multidentate TTF) and CO2 photoreduction (TAPP-Zn) centers that can serve as desired platforms to study the possible interactions between redox centers. Notably, Bi-TTCOF-Zn exhibits a high CO production rate of 11.56 µmol g-1 h-1 (selectivity, ∼100%), which is more than 2 and 6 times higher than those of Tri-TTCOF-Zn and Tetra-TTCOF-Zn, respectively. As revealed by theoretical calculations, Bi-TTCOF-Zn facilitates a more uniform distribution of energy-level orbitals, faster charge transfer, and stronger *OH adsorption/stabilization ability than those of Tri-TTCOF-Zn and Tetra-TTCOF-Zn.

RNA modifications in cancer.

Currently, more than 170 modifications have been identified on RNA. Among these RNA modifications, various methylations account for two-thirds of total cases and exist on almost all RNAs. Roles of RNA modifications in cancer are garnering increasing interest. The research on m6A RNA methylation in cancer is in full swing at present. However, there are still many other popular RNA modifications involved in the regulation of gene expression post-transcriptionally besides m6A RNA methylation. In this review, we focus on several important RNA modifications including m1A, m5C, m7G, 2'-O-Me, Ψ and A-to-I editing in cancer, which will provide a new perspective on tumourigenesis by peeking into the complex regulatory network of epigenetic RNA modifications, transcript processing, and protein translation.

Anisotropically Hybridized Porous Crystalline Li-S Battery Separators.

Anisotropically hybridized porous crystalline Li-S battery separators based on porous crystalline materials that can meet the multiple functionalities of both anodic and cathodic sides are much desired for Li-S battery yet still challenging in directional design. Here, an anisotropically hybridized separator (CPM) based on an ionic liquid-modified porphyrin-based covalent-organic framework (COF-366-OH-IL) and catalytically active metal-organic framework (Ni3 (HITP)2 ) that can integrate the lithium-polysulfides (LiPSs) adsorption/catalytic conversion and ion-conduction sites together to directionally meet the requirements of electrodes is reported. Remarkably, the-obtained separator exhibits an exceptional high Li+ transference-number (tLi+  = 0.8), ultralow polarization-voltage (<30 mV), high initial specific-capacity (921.38 mAh g-1 at 1 C), and stable cycling-performance, much superior to polypropylene and monolayer-modified separators. Moreover, theoretical calculations confirm the anisotropic effect of CPM on the anodic side (e.g., Li+ transfer, LiPSs adsorption, and anode-protection) and cathodic side (e.g., LiPSs adsorption/catalysis). This work might provide a new perspective for separator exploration.

The Pillar Effect of Large-Size Alkaline Ions on the Electrochemical Stability of Sodium Manganese Hexacyanoferrate for Sodium-Ion Batteries.

Sodium manganese hexacyanoferrate (NaMnHCF) is an attractive candidate as a cathode material for sodium-ion batteries due to its low cost and high energy density. However, its practical application is hindered by poor electrochemical stability caused by the Jahn-Teller effect of Mn and the unstable structure of NaMnHCF. Here, this paper aims to address this issue by introducing highly stable AMnHCF (where A = K, Rb, or Cs) through a facile method to composite with NaMnHCF. The findings reveal that all AMnHCFs have a "pillar effect" on the crystal structure of NaMnHCF. It is observed that the degree of pillar effect varies depending on the specific AMnHCF used. The less electrochemically inactive the alkaline ion is and the greater the degree of compositing with NaMnHCF, the more dramatic the pillar effect. KMnHCF shows limited pillar effect due to its rough composition with NaMnHCF and the loss of K+ upon (de)intercalation. RbMnHCF has lower electrochemical activity and can be better composited with NaMnHCF. On the other hand, CsMnHCF exhibits the strongest pillar effect due to the inactivation of Cs+ and the excellent coherent structure formed by CsMnHCF and NaMnHCF. This research provides a new perspective on stabilizing NaMnHCF with other alkaline elements.

14-3-3 proteins regulate photomorphogenesis by facilitating light-induced degradation of PIF3.

14-3-3s are highly conserved phosphopeptide-binding proteins that play important roles in various developmental and signaling pathways in plants. However, although protein phosphorylation has been proven to be a key mechanism for regulating many pivotal components of the light signaling pathway, the role of 14-3-3 proteins in photomorphogenesis remains largely obscure. PHYTOCHROME-INTERACTING FACTOR3 (PIF3) is an extensively studied transcription factor repressing photomorphogenesis, and it is well-established that upon red (R) light exposure, photo-activated phytochrome B (phyB) interacts with PIF3 and induces its rapid phosphorylation and degradation. PHOTOREGULATORY PROTEIN KINASES (PPKs), a family of nuclear protein kinases, interact with phyB and PIF3 in R light and mediate multisite phosphorylation of PIF3 in vivo. Here, we report that two members of the 14-3-3 protein family, 14-3-3λ and κ, bind to a serine residue in the bHLH domain of PIF3 that can be phosphorylated by PPKs, and act as key positive regulators of R light-induced photomorphogenesis. Moreover, 14-3-3λ and κ preferentially interact with photo-activated phyB and promote the phyB-PIF3-PPK complex formation, thereby facilitating phyB-induced phosphorylation and degradation of PIF3 upon R light exposure. Together, our data demonstrate that 14-3-3λ and κ work in close concert with the phyB-PIF3 module to regulate light signaling in Arabidopsis.

PM2.5 induces autophagy-dependent ferroptosis by endoplasmic reticulum stress in SH-SY5Y cells.

Fine particulate matter (PM2.5 ) has been a global environmental problem threatening public health in recent years. PM2.5 exposure was associated with an increased risk of neurodegenerative diseases related to neuronal apoptosis. Ferroptosis is a nonapoptotic form of programmed the cell death, characterized by excess iron-dependent lipid peroxidation products. Whether PM2.5 could induce ferroptosis in cells and thus be involved in its neurotoxicity is unknown. In this study, we found that PM2.5 induced endoplasmic reticulum stress, apoptosis, autophagy, and ferroptosis in neuroblastoma human neuroblastoma cells (SH-SY5Y). Interestingly, ferroptosis was the predominant form of mortality in the presence of high doses of PM2.5 exposure. In addition, the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid (4-PBA) inhibited PM2.5 -induced cellular autophagy, apoptosis, and ferroptosis. Autophagy inhibitors chloroquine (CQ) alleviated PM2.5 -induced ferroptosis but did not reverse apoptosis. We also found that inhibition of both endoplasmic reticulum stress and autophagy reversed the PM2.5 -induced increase in the expression level of cytophagy nuclear receptor coactivator 4 (NCOA4). Our results suggested that PM2.5 -induced ferroptosis in SH-SY5Y cells was autophagy-dependent ferroptosis due to endoplasmic reticulum stress, which might be associated with the elevation of iron content caused by NCOA4-mediated ferritin autophagy.

First report of leaf rot on Lonicera japonica caused by Rhizopus arrhizus in China.

Lonicera japonica is a perennial shrub that has been used since ancient times as a medicine to clear heat and detoxify poisons. Its branches (the vine of L. japonica) and unopened flower buds (honeysuckle) can be used as medicine to treat external wind heat or febrile disease fever (Shang, Pan, Li, Miao, & Ding, 2011). In July 2022, a serious disease was observed in L. japonica individuals planted in an area of experimental base of Nanjing Agricultural University (N 32°02', E 118°86'), Nanjing, Jiangsu Province, China. More than 200 Lonicera plants were surveyed, and the incidence of leaf rot in Lonicera leaves was over 80%. The initial symptoms were of chlorotic spots and gradual development of visible white mycelia and powdery substances (fungal spores) were observed on the leaves. Both the front and back of the leaves gradually appeared as brown diseased spots. Thus, a combination of multiple disease spots causes leaf wilting and the leaves eventually fall off. Leaves with typical symptoms were collected and cut into approximately 5 mm square fragments. The tissues were sterilized in 1% NaOCl for 90 s and 75% ethanol for 15 s and then washed with sterile water three times. The treated leaves were cultured on Potato Dextrose Agar (PDA) medium at 25℃. When mycelia grew around the leaf pieces, fungal plugs were collected along the outer edge of the colony and transferred to fresh PDA plates using a cork borer. Eight fungal strains with the same morphology were obtained after three rounds of subculturing. The colony was initially white with a fast growth rate, and occupied a 9-cm-diameter culture dish within 24 h. The colony turned gray-black in the later stages. After 2 days, small black sporangia spots appeared on top of the hyphae. The sporangia were yellow when immature, and black at maturity. The spores were oval with an average size of 29.6 (22.4-36.9) × 35.3 (25.8-45.2) µm (n = 50) in diameter. To identify the pathogen, fungal hyphae were scraped, and the fungal genome was extracted using a kit (BioTeke, Cat#DP2031). The internal transcribed spacer region (ITS) of the fungal genome was amplified with primers ITS1/ITS4, and the results of ITS sequencing were uploaded to the GenBank database with accession number OP984201. The phylogenetic tree was constructed using the neighbor-joining method with MEGA11 software. Phylogenetic analysis based on ITS showed that the fungus was grouped together with Rhizopus arrhizus (MT590591) and had high bootstrap support. Thus, the pathogen was identified as R. arrhizus. To verify Koch's postulates, 60 ml of a spore suspension (1×104 conidia/ml) was sprayed onto the surface of 12 healthy Lonicera plants, and the other 12 plants were sprayed with sterile water as a control. All plants were kept in the greenhouse at 25°C with 60% relative humidity. After 14 d, the infected plants showed symptoms similar to those of the original diseased plants. The strain was isolated again from the diseased leaves of artificially inoculated plants and verified as the original strain by sequencing. The results showed that R. arrhizus was the pathogen responsible for Lonicera leaf rot. Previous studies have shown that R. arrhizus causes garlic bulb rot (Zhang et al., 2022) and Jerusalem artichoke tuber rot (Yang et al., 2020). To our knowledge, this is the first report of R. arrhizus causing Lonicera leaf rot disease in China. Information regarding the identification of this fungus may be helpful for controlling the leaf rot disease.

Deep Learning-Based Speech Enhancement of an Extrinsic Fabry-Perot Interferometric Fiber Acoustic Sensor System.

To achieve high-quality voice communication technology without noise interference in flammable, explosive and strong electromagnetic environments, the speech enhancement technology of a fiber-optic external Fabry-Perot interferometric (EFPI) acoustic sensor based on deep learning is studied in this paper. The combination of a complex-valued convolutional neural network and a long short-term memory (CV-CNN-LSTM) model is proposed for speech enhancement in the EFPI acoustic sensing system. Moreover, the 3 × 3 coupler algorithm is used to demodulate voice signals. Then, the short-time Fourier transform (STFT) spectrogram features of voice signals are divided into a training set and a test set. The training set is input into the established CV-CNN-LSTM model for model training, and the test set is input into the trained model for testing. The experimental findings reveal that the proposed CV-CNN-LSTM model demonstrates exceptional speech enhancement performance, boasting an average Perceptual Evaluation of Speech Quality (PESQ) score of 3.148. In comparison to the CV-CNN and CV-LSTM models, this innovative model achieves a remarkable PESQ score improvement of 9.7% and 11.4%, respectively. Furthermore, the average Short-Time Objective Intelligibility (STOI) score witnesses significant enhancements of 4.04 and 2.83 when contrasted with the CV-CNN and CV-LSTM models, respectively.

Improved Optical Path Structure for Symmetric Demodulation Method in EFPI Fiber Optic Acoustic Sensors Using Wavelength Division Multiplexing.

This paper presents a novel improvement in the optical path structure of a three-wavelength symmetric demodulation method applied to extrinsic Fabry-Perot interferometer (EFPI) fiber optic acoustic sensors. The traditional approach of using couplers to construct the phase difference in the symmetric demodulation method is replaced with a new approach that combines the symmetric demodulation algorithm with wavelength division multiplexing (WDM) technology. This improvement addresses the issue of a suboptimal coupler split ratio and phase difference, which can affect the accuracy and performance of the symmetric demodulation method. In an anechoic chamber test environment, the symmetric demodulation algorithm implemented with the WDM optical path structure achieved a signal-to-noise ratio (SNR) of 75.5 dB (1 kHz), a sensitivity of 1104.9 mV/Pa (1 kHz), and a linear fitting coefficient of 0.9946. In contrast, the symmetric demodulation algorithm implemented with the traditional coupler-based optical path structure achieved an SNR of 65.1 dB (1 kHz), a sensitivity of 891.75 mV/Pa (1 kHz), and a linear fitting coefficient of 0.9905. The test results clearly indicate that the improved optical path structure based on WDM technology outperforms the traditional coupler-based optical path structure in terms of sensitivity, SNR, and linearity.

Hierarchical Confinement Effect with Zincophilic and Spatial Traps Stabilized Zn-Based Aqueous Battery.

Zn-based aqueous batteries (ZABs) have been regarded as promising candidates for safe and large-scale energy storage in the "post-Li" era. However, kinetics and stability problems of Zn capture cannot be concomitantly regulated, especially at high rates and loadings. Herein, a hierarchical confinement strategy is proposed to design zincophilic and spatial traps through a host of porous Co-embedded carbon cages (denoted as CoCC). The zincophilic Co sites act as preferred nucleation sites with low nucleation barriers (within 0.5 mA h cm-2), and the carbon cage can further spatially confine Zn deposition (within 5.0 mA h cm-2). Theoretical simulations and in situ/ex situ structural observations reveal the hierarchical spatial confinement by the elaborated all-in-one network (within 12 mA h cm-2). Consequently, the elaborate strategy enables a dendrite-free behavior with excellent kinetics (low overpotential of ca. 65 mV at a high rate of 20 mA cm-2) and stable cycle life (over 800 cycles), pushing forward the next-generation high-performance ZABs.

Integrated Micro Space Electrostatic Field in Aqueous Zn-Ion Battery: Scalable Electrospray Fabrication of Porous Crystalline Anode Coating.

The inhomogeneous consumption of anions and direct contact between electrolyte and anode during the Zn-deposition process generate Zn-dendrites and side reactions that can aggravate the space-charge effect to hinder the practical implementation of zinc-metal batteries (ZMBs). Herein, electrospray has been applied for the scalable fabrication (>10 000 cm2 in a batch-experiment) of hetero-metallic cluster covalent-organic-frameworks (MCOF-Ti6 Cu3 ) nanosheet-coating (MNC) with integrated micro space electrostatic field for ZMBs anode protection. The MNC@Zn symmetric cell presents ultralow overpotential (≈72.8 mV) over 10 000 cycles at 1 mAh cm-2 with 20 mA cm-2 , which is superior to bare Zn and state-of-the-art porous crystalline materials. Theoretical calculations reveal that MNC with integrated micro space electrostatic field can facilitate the deposition-kinetic and homogenize the electric field of anode to significantly promote the lifespan of ZMBs.

Splicing factor derived circular RNA circCAMSAP1 accelerates nasopharyngeal carcinoma tumorigenesis via a SERPINH1/c-Myc positive feedback loop.

BACKGROUND: Circular RNAs play an important role in tumor genesis and progression, but they have not been sufficiently studied in patients with nasopharyngeal carcinoma (NPC). METHODS: The circular RNA, circCAMSAP1, was screened in NPC cells by RNA sequencing analysis. The expression of circCAMSAP1 in NPC tissues was examined by real-time quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization. Wound-healing, transwell, MTT and flow cytometry assays, and nude mouse tumor models were used to explore the effect of circCAMSAP1 on proliferation and metastasis of NPC in vitro or in vivo. The downstream proteins regulated by circCAMSAP1 were screened using mass spectrometry. The interaction between circCAMSAP1 and the SERPINH1 mRNA was identified using the circular RNA immunoprecipitation method and the luciferase reporter assay. The interaction between SERPINH1 and transcription factor c-Myc was verified through Co-immunoprecipitation (Co-IP) and immunofluorescence. The effect of c-Myc on the generation of circCAMSAP1 was examined through RT-qPCR and chromatin immunoprecipitation. Finally, the splicing factors that promote the production of circCAMSAP1 were explored by RT-qPCR and RNA immunoprecipitation (RIP). RESULTS: We found that circCAMSAP1 was highly expressed in NPC tissues and promoted NPC proliferation and metastasis. Additionally, circCAMSAP1 promoted SERPINH1 expression through improved SERPINH1 mRNA stability by binding to the 3'-untranslated region (3'UTR) of SERPINH1. Highly expressed SERPINH1 reduced the ubiquitination-degradation rate of c-Myc, causing increased tumorigenesis. Meanwhile, c-Myc, cooperating with splicing factor 10 (SRSF10), could also promote CAMSAP1 pre-mRNA transcription and back-splicing, forming a positive feedback of circCAMSAP1 production, resulting in the proliferation and metastasis of NPC. CONCLUSIONS: Our findings revealed that circCAMSAP1 promotes NPC proliferation and metastasis by binding to the 3'UTR of SERPINH1, suggesting that the positive feedback of circCAMSAP1-SERPINH1-c-Myc may serve as a prognostic biomarker or therapeutic target in patients with NPC.

Circular RNA circPVT1 promotes nasopharyngeal carcinoma metastasis via the ß-TrCP/c-Myc/SRSF1 positive feedback loop.

BACKGROUND: Circular RNAs (circRNAs) act as gene expression regulators and are involved in cancer progression. However, their functions have not been sufficiently investigated in nasopharyngeal carcinoma (NPC). METHODS: The expression profiles of circRNAs in NPC cells within different metastatic potential were reanalyzed. Quantitative reverse transcription PCR and in situ hybridization were used to detect the expression level of circPVT1 in NPC cells and tissue samples. The association of expression level of circPVT1 with clinical properties of NPC patients was evaluated. Then, the effects of circPVT1 expression on NPC metastasis were investigated by in vitro and in vivo functional experiments. RNA immunoprecipitation, pull-down assay and western blotting were performed to confirm the interaction between circPVT1 and ß-TrCP in NPC cells. Co-immunoprecipitation and western blotting were performed to confirm the interaction between ß-TrCP and c-Myc in NPC cells. RESULTS: We find that circPVT1, a circular RNA, is significantly upregulated in NPC cells and tissue specimens. In vitro and in vivo experiments showed that circPVT1 promotes the invasion and metastasis of NPC cells. Mechanistically, circPVT1 inhibits proteasomal degradation of c-Myc by binding to ß-TrCP, an E3 ubiquiting ligase. Stablization of c-Myc by circPVT1 alters the cytoskeleton remodeling and cell adhesion in NPC, which ultimately promotes the invasion and metastasis of NPC cells. Furthermore, c-Myc transcriptionally upregulates the expression of SRSF1, an RNA splicing factor, and recruits SRSF1 to enhance the biosynthesis of circPVT1 through coupling transcription with splicing, which forms a positive feedback for circPVT1 production. CONCLUSIONS: Our results revealed the important role of circPVT1 in the progression of NPC through the ß-TrCP/c-Myc/SRSF1 positive feedback loop, and circPVT1 may serve as a prognostic biomarker or therapeutic target in patients with NPC.

Long non-coding RNAs are involved in alternative splicing and promote cancer progression.

Alternative splicing (AS) is a key process in which precursor RNAs produce different mature RNAs, and the disorder of AS is a key factor in promoting cancer development. Compared with coding RNA, studies on the functions of long non-coding RNAs (lncRNAs) are far from enough. In fact, lncRNA is an important participant and regulator in the process of AS. On the one hand, lncRNAs regulate cancer progression as AS products of precursor messenger RNA (mRNA), but on the other hand, precursor lncRNA generates cancer-related abnormal splicing variants through AS. In addition, lncRNAs directly or indirectly regulate the AS events of downstream target genes, thus affecting the occurrence and development of cancer. Here, we reviewed how lncRNAs regulate AS and influence oncogenesis in different ways.