Drug resistance mechanisms and treatment strategies mediated by Ubiquitin-Specific Proteases (USPs) in cancers: new directions and therapeutic options.

Drug resistance represents a significant obstacle in cancer treatment, underscoring the need for the discovery of novel therapeutic targets. Ubiquitin-specific proteases (USPs), a subclass of deubiquitinating enzymes, play a pivotal role in protein deubiquitination. As scientific research advances, USPs have been recognized as key regulators of drug resistance across a spectrum of treatment modalities, including chemotherapy, targeted therapy, immunotherapy, and radiotherapy. This comprehensive review examines the complex relationship between USPs and drug resistance mechanisms, focusing on specific treatment strategies and highlighting the influence of USPs on DNA damage repair, apoptosis, characteristics of cancer stem cells, immune evasion, and other crucial biological functions. Additionally, the review highlights the potential clinical significance of USP inhibitors as a means to counter drug resistance in cancer treatment. By inhibiting particular USP, cancer cells can become more susceptible to a variety of anti-cancer drugs. The integration of USP inhibitors with current anti-cancer therapies offers a promising strategy to circumvent drug resistance. Therefore, this review emphasizes the importance of USPs as viable therapeutic targets and offers insight into fruitful directions for future research and drug development. Targeting USPs presents an effective method to combat drug resistance across various cancer types, leading to enhanced treatment strategies and better patient outcomes.

Effects of Electric Field on Chemical Looping Combustion: A DFT Study of CO Oxidation on CuO (111) Surface.

Chemical looping combustion (CLC) is a promising and novel technology for carbon dioxide (CO2) capture with a relatively low energy consumption and cost. CuO, one of the most attractive oxygen carriers (OCs) for carbon dioxide (CO) oxidation, suffers from sintering and agglomeration during the reduction process. Applying an electric field (EF) may promote the CO oxidation process on the CuO surface, which could mitigate sintering and agglomeration by decreasing operating temperatures with negligible combustion efficiency loss. This study performs density functional theory (DFT) simulations to investigate the effects of EF on the oxidation of CO on the CuO (111) surface. The results indicate that both the orientation and strength of the EF can significantly affect the oxidation characteristics of CO on the CuO (111) surface such as total reaction energy, energy barriers of reactions, CO adsorption, and CO2 desorption. For the first time, this study reveals the role of EF in enhancing CO oxidation through CLC processes via first-principle calculations. Such findings could provide new strategies to improve the performance of CLC processes.

Role of blood flow in endothelial functionality: a review.

Endothelial cells, located on the surface of blood vessel walls, are constantly stimulated by mechanical forces from the blood flow. The mechanical forces, i.e., fluid shear stress, induced by the blood flow play a pivotal role in controlling multiple physiological processes at the endothelium and in regulating various pathways that maintain homeostasis and vascular function. In this review, research looking at different blood fluid patterns and fluid shear stress in the circulation system is summarized, together with the interactions between the blood flow and the endothelial cells. This review also highlights the flow profile as a response to the configurational changes of the endothelial glycocalyx, which is less revisited in previous reviews. The role of endothelial glycocalyx in maintaining endothelium health and the strategies for the restoration of damaged endothelial glycocalyx are discussed from the perspective of the fluid shear stress. This review provides a new perspective regarding our understanding of the role that blood flow plays in regulating endothelial functionality.

Theoretical exploration on the performance of single and dual-atom Cu catalysts on the CO2 electroreduction process: a DFT study.

Carbon dioxide (CO2) electroreduction by metal-nitrogen-doped carbon (MNC) catalysts is a promising and efficient method to mitigate global warming by converting CO2 molecules to value-added chemicals. In this research, we systematically studied the behaviours of single and dual-atom Cu catalysts during the CO2 electroreduction process using density functional theory (DFT) calculations. Two structures, i.e., CuNC-4-pyridine and CuCuNC-4a, were found to be beneficial for C2 chemical generation with relatively high stabilities. Subsequently, we explored the detailed pathways of key products (CO, HCOOH, CH3OH, CH4, C2H6O, C2H4 and C2H6) during CO2 electroreduction on CuNC-4-pyridine and CuCuNC-4a. This research reveals the mechanisms of key product formation during CO2 electroreduction on CuNC-4-pyridine and CuCuNC-4a, which would provide important insights to guide the design of MNC catalysts with low limiting potentials and high product selectivity.

Posterior Displacement of L1 May be a Risk Factor for Proximal Junctional Kyphosis After Adult Spinal Deformity Correction.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Overcorrection in adult spinal deformity (ASD) surgery may lead to proximal junctional kyphosis (PJK) because of posterior spinal displacement. The aim of this paper is to determine if the L1 position relative to the gravity line (GL) is associated with PJK. METHODS: ASD patients fused from the lower thoracic spine to sacrum by 4 spine surgeons at our hospital were retrospectively studied. Lumbar-only and upper thoracic spine fusions were excluded. Spinopelvic parameters, the L1 plumb line (L1PL), L1 distance to the GL (L1-GL), and Roussouly type were measured. RESULTS: One hundred fourteen patients met inclusion criteria (63 patients with PJK, 51 without). Mean age and follow up was 65.51 and 3.39 years, respectively. There was no difference between the PJK and the non-PJK groups in baseline demographics, pre-operative and immediate post-operative pelvic incidence-lumbar lordosis mismatch, sagittal vertical axis, or coronal Cobb. The immediate postoperative L1-GL was -7.24 cm in PJK and -3.45 cm in non-PJK (P < 0.001), L1PL was 1.71 cm in PJK and 3.07 cm in non-PJK (P = 0.004), and PT (23.76° vs 18.90°, P = 0.026) and TK (40.56° vs 31.39°, P < 0.001) were larger in PJK than in non-PJK. After univariate and multivariate analyses, immediate postoperative TK and immediate postoperative L1-GL were independent risk factors for PJK without collinearity. CONCLUSIONS: A dorsally displaced L1 relative to the GL was associated with an increased risk of PJK after ASD surgery. The postoperative L1-GL distance may be a factor to consider during ASD surgery.

Integrated Analysis of Multiomics Data Identified Molecular Subtypes and Oxidative Stress-Related Prognostic Biomarkers in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is a glioma in IV stage, which is one of the most common primary malignant brain tumors in adults. GBM has the characters of high invasiveness, high recurrence rate, and low survival rate and with a poor prognosis. GBM implicates various genetic changes and epigenetic and gene transcription disorders, which are crucial in developing GBM. With the progression and enhancement of high-throughput sequencing technologies, the acquirement and administering approaches of diverse biological omics data on distinctive levels are developing more advanced. However, the research of GBM with multiomics remains largely unknown. We identified GBM-related molecular subtypes by integrated multiomics data and exploring the connections of gene copy number variation (CNV) and methylation gene (MET) change data. The expression of CNV and MET genes was examined through cluster integration analysis. The present study confirmed three clusters (iC1, iC2, and iC3) with distinctive prognosis and molecule peculiarities. We also recognized three oxidative stress protecting molecules (OSMR, IGFBP6, and MYBPH) by contrasting gene expression, MET, and CNV in the three subtypes. OSMR, IGFBP6, and MYBPH were differentially expressed in the clusters, suggesting they might be recognized as characteristic markers for the three clusters in GBM. Through integrative investigation of genomics, epigenomics, and transcriptomics, we offer novel visions into the multilayered molecules of GBM and facilitate the accuracy remedy for GBM sufferers.

Molecular dynamics simulation: A new way to understand the functionality of the endothelial glycocalyx.

Endothelial glycocalyx (EG) is a carbohydrate-rich layer which lines the lumen side of blood vessel walls. The EG layer is directly exposed to blood flow. The unique physiological location and its strongly coupled interaction with blood flow allow the EG layer to modulate microvascular mass transport and to sense and transmit mechanical signals from the passing blood. Molecular dynamics (MD) simulation is a computational method which focuses on atomic/molecular behavior at the microscale. The last two decades have witnessed a substantial increase in number and a broadening in scope regarding applications of MD in a wide spectrum of areas, including EG-related research. In this mini-review, MD works which solve EG-related problems and provide new insights into the functionality of EG are considered. Challenges of the MD method in EG research are articulated, and the future of MD in solving EG-related problems is also evaluated.

Upper instrumented vertebra-femoral angle and correlation with proximal junctional kyphosis in adult spinal deformity.

INTRODUCTION: Although matching lumbar lordosis (LL) with pelvic incidence (PI) is an important surgical goal for adult spinal deformity (ASD), there is concern that overcorrection may lead to proximal junctional kyphosis (PJK). We introduce the upper instrumented vertebra-femoral angle (UIVFA) as a measure of appropriate postoperative position in the setting of lower thoracic to pelvis surgical correction for patients with sagittal imbalance. We hypothesize that a more posterior UIV position in relation to the center of the femoral head is associated with an increased risk of PJK given compensatory hyperkyphosis above the UIV. METHODS: In this retrospective cohort study, adult patients undergoing lower thoracic (T9-T12) to pelvis correction of ASD with a minimum of 2-year follow-up were included. UIVFA was measured as the angle subtended by a line from the UIV centroid to the femoral head center to the vertical axis. Patients who developed PJK and those who did not were compared with preoperative and postoperative UIVFA as well as change between postoperative and preoperative UIVFA (deltaUIVFA). RESULTS: Of 119 patients included with an average 3.6-year follow-up, 51 (42.9%) had PJK and 24 (20.2%) had PJF. Patients with PJK had significantly higher postoperative UIVFA (12.6 ± 4.8° vs. 9.4 ± 6.6°, p = 0.04), deltaUIVFA (6.1 ± 7.6° vs. 2.1 ± 5.6°, p < 0.01), postoperative pelvic tilt (27.3 ± 9.2 vs. 23.3 ± 11, p = 0.04), postoperative lumbar lordosis (47.7 ± 13.9° vs. 42.4 ± 13.1, p = 0.04) and postoperative thoracic kyphosis (44.9 ± 13.2 vs. 31.6 ± 18.8) than patients without PJK. With multivariate logistic regression, postoperative UIVFA and deltaUIVFA were found to be independent risk factors for PJK (p < 0.05). DeltaUIVFA was found to be an independent risk factor for PJF (p < 0.05). A receiver operating characteristic (ROC) curve for UIVFA as a predictor for PJK was established with an area under the curve of 0.67 (95% CI 0.59-0.76). Per the Youden index, the optimal UIVFA cut-off value is 11.5 degrees. CONCLUSION: The more posterior the UIV is from the femoral head center after lower thoracic to pelvis surgical correction for ASD, the more patients are at risk for PJK. The greater the magnitude of posterior translation of the UIV from the femoral head center from preop to postop, the greater the likelihood for PJF.

Bursaphelenchus xylophilus detection and analysis system based on CRISPR - Cas12.

Pine wilt disease is caused by the pine wood nematode (Bursaphelenchus xylophilus) and leads to wilting and death of pines. It is one of the most damaging diseases of pines worldwide. Therefore, accurate and rapid detection methods are of great importance for the control of B. xylophilus. Traditional detection methods have some problems, such as being time-consuming and requiring expensive instruments. In this study, the loop-mediated isothermal amplification (LAMP) and clustered regularly interspaced short palindromic repeats (CRISPR) were used to establish a set of intelligent detection and analysis system for B. xylophilus, called LAMP-CRISPR/Cas12a analysis, which integrated field sampling, rapid detection and intelligent control analysis. The process can be completed within 1 hour, from sample pretreatment and detection to data analysis. Compared with the single LAMP method, the LAMP-CRISPR/Cas12a assay uses species-specific fluorescence cleavage to detect target amplicons. This process confirms the amplicon identity, thereby avoiding false-positive results from non-specific amplicons, and the large amounts of irrelevant background DNA do not interfere with the reaction. The LAMP-CRISPR/Cas12a assay was applied to 46 pine wood samples and the samples carrying B. xylophilus nematodes were successfully identified. To meet the needs of different environments, we designed three methods to interpret the data: 1) naked eye interpretation; 2) lateral flow biosensor assay; and 3) integrated molecular analysis system to standardize and intellectualize the detection process. Application of the B. xylophilus detection and analysis system will reduce the professional and technical requirements for the operating environment and operators and help to ensure the accuracy of the detection results, which is important in grass-root B. xylophilus detection institutions.

Biomechanical properties of endothelial glycocalyx: An imperfect pendulum.

Endothelial glycocalyx plays a crucial role in hemodynamics in health and disease, yet studying it is met by multiple technical hindrances. We attempted to outline our views on some biomechanical properties of endothelial glycocalyx, which are potentially amenable to mathematical modeling. We start with the null-hypothesis ascribing to glycocalyx the properties of a pendulum and reject this hypothesis on the grounds of multiple obstacles for pendulum behavior, such as rich decoration with flexible negatively charged side-chains, variable length and density, fluid fixation to the plasma membrane. We next analyze the current views on membrane attachments to the cortical actin web, its pulsatile contraction-relaxation cycles which rebound to the changes in tension of the plasma membrane. Based on this, we consider the outside-in signaling, the basis for mechanotransduction, and the dampening action of the inside-out signaling. The aperiodic oscillatory motions of glycocalyx and cortical actin web underlie our prediction of two functional pacemakers. We next advance an idea that the glycocalyx, plasma membrane, and cortical actin web represent a structure-functional unit and propose the concept of tensegrity model. Finally, we present our recent data suggesting that erythrocytes are gliding or hovering and rotating over the surface of intact glycocalyx, whereas the rotational and hovering components of their passage along the capillaries are lost when glycocalyx of either is degraded. These insights into the mechanics of endothelial glycocalyx motions may be of value in crosspollination between biomechanics, physiology, and pathophysiology for deeper appreciation of its rich untapped resources in health and pharmacotherapy in disease.

Understanding the Role of Endothelial Glycocalyx in Mechanotransduction via Computational Simulation: A Mini Review.

Endothelial glycocalyx (EG) is a forest-like structure, covering the lumen side of blood vessel walls. EG is exposed to the mechanical forces of blood flow, mainly shear, and closely associated with vascular regulation, health, diseases, and therapies. One hallmark function of the EG is mechanotransduction, which means the EG senses the mechanical signals from the blood flow and then transmits the signals into the cells. Using numerical modelling methods or in silico experiments to investigate EG-related topics has gained increasing momentum in recent years, thanks to tremendous progress in supercomputing. Numerical modelling and simulation allows certain very specific or even extreme conditions to be fulfilled, which provides new insights and complements experimental observations. This mini review examines the application of numerical methods in EG-related studies, focusing on how computer simulation contributes to the understanding of EG as a mechanotransducer. The numerical methods covered in this review include macroscopic (i.e., continuum-based), mesoscopic [e.g., lattice Boltzmann method (LBM) and dissipative particle dynamics (DPD)] and microscopic [e.g., molecular dynamics (MD) and Monte Carlo (MC) methods]. Accounting for the emerging trends in artificial intelligence and the advent of exascale computing, the future of numerical simulation for EG-related problems is also contemplated.

Comprehensive Analysis of CD163 as a Prognostic Biomarker and Associated with Immune Infiltration in Glioblastoma Multiforme.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common and aggressive primary malignancy in adults with high aggression. The prognosis of GBM patients is poor. There is a critical need for novel biomarkers for the prognosis and therapy of GBM. METHODS: Differentially expressed genes (DEGs) in GBM were screened using TCGA cohort. Univariate and multivariate Cox regression analyses were performed on DEGs to identify the optimal prognosis-related genes. qRT-PCR was performed to verify the result. RESULTS: A total of 5216 DEGs, including 2785 upregulated and 2458 downregulated genes, were obtained. Enrichment analysis revealed that these DEGs were mainly involved in the p53 signaling pathway and cell cycle, immune response, and MAPK signaling pathways. Moreover, the top 50 DEGs were associated with drug resistance or drug sensitivity. Prognosis analysis revealed that GBM patients with a high expression of CD163 and CHI3L2 had a poor overall survival, prognosis-free survival, and disease-specific survival. The univariate and multivariate analyses revealed that CD163 and age were independent factors affecting the prognosis of GBM patients. A validation study revealed that CD163 was upregulated in GBM tissues and associated with poor overall survival. Moreover, further analysis revealed that CD163 showed significant correlation with immune cells, immune biomarkers, chemokines, and chemokine receptors. We also identified several CD163-associated kinase, miRNA, and transcription factor targets in GBM, including LCK, miR-483, and ELF1. CONCLUSIONS: In conclusion, our study suggested CD163 as a prognostic biomarker and associated it with immune infiltration in GBM.

SUMOylation of IGF2BP2 promotes vasculogenic mimicry of glioma via regulating OIP5-AS1/miR-495-3p axis.

Rationale: Glioma is the most common primary malignant tumor of human central nervous system, and its rich vascular characteristics make anti-angiogenic therapy become a therapeutic hotspot. However, the existence of glioma VM makes the anti-angiogenic therapy ineffective. SUMOylation is a post-translational modification that affects cell tumorigenicity by regulating the expression and activity of substrate proteins. Methods: The binding and modification of IGF2BP2 and SUMO1 were identified using Ni2+-NTA agarose bead pull-down assays, CO-IP and western blot; and in vitro SUMOylation assays combined with immunoprecipitation and immunofluorescence staining were performed to explore the detail affects and regulations of the SUMOylation on IGF2BP2. RT-PCR and western blot were used to detect the expression levels of IGF2BP2, OIP5-AS1, and miR-495-3p in glioma tissues and cell lines. CCK-8 assays, cell transwell assays, and three-dimensional cell culture methods were used for evaluating the function of IGF2BP2, OIP5-AS1, miR-495-3p, HIF1A and MMP14 in biological behaviors of glioma cells. Meantime, RIP and luciferase reporter assays were used for inquiring into the interactions among IGF2BP2, OIP5-AS1, miR-495-3p, HIF1A and MMP14. Eventually, the tumor xenografts in nude mice further as certained the effects of IGF2BP2 SUMOylation on glioma cells. Results: This study proved that IGF2BP2 mainly binds to SUMO1 and was SUMOylated at the lysine residues K497, K505 and K509 sites, which can be reduced by SENP1. SUMOylation increased IGF2BP2 protein expression and blocked its degradation through ubiquitin-proteasome pathway, thereby increasing its stability. The expressions of IGF2BP2 and OIP5-AS1 were up-regulated and the expression of miR-495-3p was down-regulated in both glioma tissues and cells. IGF2BP2 enhances the stability of OIP5-AS1, thereby increasing the binding of OIP5-AS1 to miR-495-3p, weakening the binding of miR-495-3p to the 3'UTR of HIF1A and MMP14 mRNA, and ultimately promoting the formation of VM in glioma. Conclusions: This study first revealed that SUMOylation of IGF2BP2 regulated OIP5-AS1/miR-495-3p axis to promote VM formation in glioma cells and xenografts growth in nude mice, providing a new idea for molecular targeted therapy of glioma.

KLF11 Expression Predicts Poor Prognosis in Glioma Patients.

PURPOSE: Glioma is a primary intracranial malignant tumor with high recurrence and mortality rates. It is very important to study the prognostic factors. KLF11 can function as an oncogene or a tumor suppressor, depending on the tumor and tissue types and the cancer stage. In this study, we aimed to determine whether KLF11 expression is related to the overall survival of glioma patients. PATIENTS AND METHODS: We investigated KLF11 expression in 116 glioma patients with different grades using Western blot and immunohistochemistry assay. We analyzed the patients with different glioma grades and KLF11 expression levels by Kaplan-Meier survival curves. Independent prognostic factors for poor overall survival were identified by univariate and multivariate analyses. RESULTS: There were 37 patients in KLF11 low expression group and 79 patients in high expression group. There was no difference in gender, age, tumor diameter or tumor location between two groups. The patients in KLF11 high expression group had higher ECOG score (P =0.025) and higher WHO grades (P =0.029). Western blot and immunohistochemistry assay showed KLF11 expression was significantly upregulated in glioma groups compared with normal brain tissues group (P < 0.05), and the expression in grades III-IV was significantly higher than those in grades I-II (P < 0.05). Kaplan-Meier survival curve analysis showed high KLF11 expression tended to reduce the overall survival (P < 0.05). After univariate and multivariate analyses, KLF11 expression (P =0.003) and age (P =0.007) were independent prognostic factors for poor survival in glioma patients. CONCLUSION: KLF11 expression was increased in glioma tissues, and high KLF11 expression was associated with poor prognosis. KLF11 expression was an independent prognostic factor for poor survival in glioma patients. KLF11 may serve as a novel prognostic marker for gliomas and as a novel treatment target.

Cross talk between endothelial and red blood cell glycocalyces via near-field flow.

Vascular endothelial cells and circulating red blood cell (RBC) surfaces are both covered by a layer of bushy glycocalyx. The interplay between these glycocalyx layers is hardly measurable and insufficiently understood. This study aims to investigate and qualify the possible interactions between the glycocalyces of RBCs and endothelial cells using mathematical modeling and numerical simulation. Dissipative particle dynamics (DPD) simulations are conducted to investigate the response of the endothelial glycocalyx (EG) to varying ambient conditions. A two-compartment model including EG and flow and a three-compartment model comprising EG, RBC glycocalyx, and flow are established. The two-compartment analysis shows that a relatively fast flow is associated with a predominantly bending motion of the EG, whereas oscillatory motions are predominant in a relatively slow flow. Results show that circulating RBCs cause the contactless deformation of EG. Its deformation is dependent on the chain layout, chain length, bending stiffness, RBC-to-EG distance, and RBC velocities. Specifically, shorter EG chains or RBC-to-EG distance leads to greater relative deflections of EG. Deformation of EG is enhanced when the EG chains are rarefied or RBCs move faster. The bending stiffness maintains stretching conformation of EG. Moreover, a compact EG chain layout and shedding EG chains disturb the neighboring flow field, causing disordered flow velocity distributions. In contrast, the movement of EG chains on RBC surfaces exerts a marginal driving force on RBCs. The DPD method is used for the first time, to our knowledge, in the three-compartment system to explore the cross talk between EG and RBC glycocalyx. This study suggests that RBCs drive the EG deformation via the near-field flow, whereas marginal propulsion of RBCs by the EG is observed. These new, to our knowledge, findings provide a new angle to understand the roles of glycocalyx in mechanotransduction and microvascular permeability and their perturbations under idealized pathophysiologic conditions associated with EG degradation.

The Prognostic Role and Nomogram Establishment of a Novel Prognostic Score Combining with Fibrinogen and Albumin Levels in Patients with WHO Grade II/III Gliomas.

PURPOSE: World Health Organization (WHO) Grades II and III gliomas [also known as low grade gliomas (LGGs)] displayed different malignant behaviors and survival outcomes compared to Grade IV gliomas. This study aimed to identify the prognostic predictive value of a novel cumulative prognostic score [combined with fibrinogen and albumin levels (FA score)], establish and validate a point-based nomogram in LGG patients. PATIENTS AND METHODS: A total of 91 patients who underwent total glioma resection at Shengjing Hospital of China Medical University between 2011 and 2013 were enrolled to establish a prognostic nomogram. All patients were histologically diagnosed as grades II/III, and never received radiotherapy or chemotherapy before surgery. Data collection included patient characteristics, clinicopathological factors, and preoperative hematology results. The performance of the nomogram was subsequently validated by the concordance index (c-index), calibration curve, and receiver operating characteristic (ROC) curve. RESULTS: The FA score was negatively associated with the overall survival (OS) of LGG patients (p < 0.001). The results of multivariate analysis showed that FA score [p = 0.006, HR = 1.92, 95% confidence interval (CI): 1.21-3.05], age (p = 0.002, HR = 3.014, 95% CI:1.52-5.97), and white blood count (p < 0.001, HR = 4.24, 95% CI: 2.08-8.67) were independent prognostic factors for overall survival (OS). The study established a nomogram to predict OS with a c-index of 0.783 (95% CI, 0.72-0.84). CONCLUSION: FA score might be a potential prognostic biomarker for LGG patients, and a reliable point-based nomogram will help clinicians to decide on the best treatment plans.

Serum levels of the IgA isotype switch factor TGF-ß1 are elevated in patients with COVID-19.

We previously observed enhanced immunoglobulin A (IgA) responses in severe COVID-19, which might confer damaging effects. Given the important role of IgA in immune and inflammatory responses, the aim of this study was to investigate the dynamic response of the IgA isotype switch factor TGF-ß1 in COVID-19 patients. We observed, in a total of 153 COVID-19 patients, that the serum levels of TGF-ß1 were increased significantly at the early and middle stages of COVID-19, and correlated with the levels of SARS-CoV-2-specific IgA, as well as with the APACHE II score in patients with severe disease. In view of the genetic association of the TGF-ß1 activator THBS3 with severe COVID-19 identified by the COVID-19 Host Genetics Initiative, this study suggests TGF-ß1 may play a key role in COVID-19.

SP1-induced overexpression of LINC00520 facilitates non-small cell lung cancer progression through miR-577/CCNE2 pathway and predicts poor prognosis.

Long noncoding RNAs (lncRNAs) have gained much attention in the past few years. Long intergenic non-protein coding RNA 520 (LINC00520) was one of the newly discovered lncRNA which has been demonstrated to be dysregulated in several cancers. So far, the function and mechanism of LINC00520 in non-small cell lung cancer (NSCLC) are unclear. In this paper, our group first showed that LINC00520 level was elevated in non-small cell lung cancer (NSCLC) tissue and cells. In addition, SP1 could bind directly to the promoter region of LINC00520 and thus promote its transcription. Increased LINC00520 was distinctly correlated with advanced tumor stage and shorter survival time in NSCLC patients. Further functional investigations provided evidences that forced down regulation of LINC00520 inhibited NSCLC cell proliferation, invasion, metastasis and EMT, while contributing to cells apoptosis. Mechanistically, we found that LINC00520 serving as a competing endogenous RNA to be involved in the modulation of miR-577 expressions, and thus affected the expression of CCNE2 which was a target gene of miR-577. Moreover, in NSCLC cells with si-LINC00520, up regulation of CCNE2 led to an increase of cell growth and invasion. Taken together, LINC00520 displayed its tumor-promotive roles through modulating the miR-577/CCNE2 axis, highlighting a potential therapeutic strategy for NSCLC patients.