Clinical usefulness of the lymphocyte-to-monocyte ratio and aggregate index of systemic inflammation in patients with esophageal cancer: a retrospective cohort study.

BACKGROUND: Multiple perioperative inflammatory markers are considered important factors affecting the long-term survival of esophageal cancer (EC) patients. Hematological parameters, whether single or combined, have high predictive value. AIM: To investigate the inflammatory status of patients with preoperative EC using blood inflammatory markers, and to establish and validate competing risk nomogram prediction models for overall survival (OS) and progression-free survival (PFS) in EC patients. METHODS: A total of 508 EC patients who received radical surgery (RS) treatment in The First Affiliated Hospital of Zhengzhou University from August 5, 2013, to May 1, 2019, were enrolled and randomly divided into a training cohort (356 cases) and a validation cohort (152 cases). We performed least absolute shrinkage and selection operator (LASSO)-univariate Cox- multivariate Cox regression analyses to establish nomogram models. The index of concordance (C-index), time-dependent receiver operating characteristic (ROC) curves, time-dependent area under curve (AUC) and calibration curves were used to evaluate the discrimination and calibration of the nomograms, and decision curve analysis (DCA) was used to evaluate the net benefit of the nomograms. The relative integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were calculated to evaluate the improvement in predictive accuracy of our new model compared with the AJCC staging system and another traditional model. Finally, the relationship between systemic inflammatory response markers and prognostic survival was explored according to risk plot, time-dependent AUC, Kaplan-Meier and restricted cubic spline (RCS). RESULTS: Based on the multivariate analysis for overall survival (OS) in the training cohort, nomograms with 10 variables, including the aggregate index of systemic inflammation (AISI) and lymphocyte-to-monocyte ratio (LMR), were established. Time-dependent ROC, time-dependent AUC, calibration curves, and DCA showed that the 1-, 3-, and 5 year OS and PFS probabilities predicted by the nomograms were consistent with the actual observations. The C-index, NRI, and IDI of the nomograms showed better performance than the AJCC staging system and another prediction model. Moreover, risk plot, time-dependent AUC, and Kaplan-Meier showed that higher AISI scores and lower LMR were associated with poorer prognosis, and there was a nonlinear relationship between them and survival risk. CONCLUSION: AISI and LMR are easy to obtain, reproducible and minimally invasive prognostic tools that can be used as markers to guide the clinical treatment and prognosis of patients with EC.

Fractionalized Prethermalization in a Driven Quantum Spin Liquid.

Quantum spin liquids subject to a periodic drive can display fascinating nonequilibrium heating behavior because of their emergent fractionalized quasiparticles. Here, we investigate a driven Kitaev honeycomb model and examine the dynamics of emergent Majorana matter and Z_{2} flux excitations. We uncover a distinct two-step heating profile-dubbed fractionalized prethermalization-and a quasistationary state with vastly different temperatures for the matter and the flux sectors. We argue that this peculiar prethermalization behavior is a consequence of fractionalization. Furthermore, we discuss an experimentally feasible protocol for preparing a zero-flux initial state of the Kiteav honeycomb model with a low energy density, which can be used to observe fractionalized prethermalization in quantum information processing platforms.

Exact Solution for the Interacting Kitaev Chain at the Symmetric Point.

The Kitaev chain model with a nearest neighbor interaction U is solved exactly at the symmetry point Δ=t and chemical potential µ=0 in an open boundary condition. By applying two Jordan-Wigner transformations and a spin rotation, such a symmetric interacting model is mapped onto a noninteracting fermion model, which can be diagonalized exactly. The solutions include a topologically nontrivial phase at |U|t. The two phases are related by dualities. Quantum phase transitions in the model are studied with the help of the exact solution.

Multidisciplinary diagnosis and treatment model based on a retrospective cohort study: Pulmonary function and prognosis quality of life in severe COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease worsening airflow limitation. OBJECTIVE: To explore pulmonary function rehabilitation, life quality and prognosis in patients with severe COPD. METHODS: Between February 2018 and August 2021, 150 patients with severe COPD cured in our hospital were arbitrarily assigned into the control group (n= 75) and study group (n= 75). The control group received routine treatment and the research group received multidisciplinary diagnosis and treatment. The body mass index, airflow obstruction, dyspnea and exercise (BODE), pulmonary function, the number of acute attacks, 6-minute walking distance (6MWD), Borg score and life quality were compared. RESULTS: There was no remarkable difference in BODE score before treatment (P> 0.05). During the 2- and 6-month following treatment, the BODE score of the study group was lower (P< 0.05). In the study group, FEV1 percentage of the predicted value, forced expiratory volume in one second (PPO-FEV1) and the percentage of forced expiratory volume in one second/forced vital capacity (FEV1/FVC) in the first second were higher (P< 0.05). In the study group, there were fewer acute attacks (P< 0.05). After treatment, the 6MWD of the study group following 2- and 6-month treatment was higher (P< 0.05). The Borg scores of the study group at 2- and 6-months after treatment were lower (P< 0.05). There were no remarkable differences in the score of life quality before treatment (P> 0.05), however, the symptom score, activity score, influence score and total score of the study group were lower after the treatment (P< 0.05). CONCLUSION: The application of multidisciplinary diagnosis and treatment model can promote the rehabilitation of pulmonary function of patients with severe COPD, improve their prognosis, slow down the development of the disease and enhance their life quality.

Collective effects in an incompressible electronic liquid.

Starting from Landau's kinetic equation, we show that an electronic liquid in d = 2, 3 spatial dimensions depicted by a Landau-type effective theory will become incompressible on condition that the Landau parameters satisfy either (i) [Formula: see text] or (ii) [Formula: see text]. Condition (i) is the Pomeranchuk instability in the current channel and suggests a quantum spin liquid (QSL) state with a spinon Fermi surface; while condition (ii) means that the strong repulsion in the charge channel leads to a conventional charge and thermal insulator. In the collisionless regime (ωτ ≫ 1) and the hydrodynamic regime (ωτ ≪ 1), the zero and first sound modes have been studied and classified by symmetries, including the longitudinal and transverse modes in d = 2, 3 and the higher angular momentum modes in d = 3. The sufficient (and/or necessary) conditions of these collective modes have been revealed. It has been demonstrated that some of these collective modes will behave in quite different manners under incompressibility condition (i) or (ii). Possible nematic QSL states and a hierarchy structure for gapless QSL states have been proposed in d = 3.

Development and validation of a prognostic nomogram for breast cancer patients who underwent chemoradiotherapy and surgery: a retrospective cohort study based on the SEER database and two Chinese cohorts.

There is no strong evidence indicating the optimal treatment for breast cancer (BC) and no specific prognostic model. The aim of this study was to establish nomograms to predict the overall survival (OS) of BC patients receiving chemoradiotherapy and surgery, thereby quantifying survival benefits and improving patient management. A total of 1877 patients with primary nonmetastatic BC who received chemoradiotherapy and surgery from 2010 to 2019 were identified from the Surveillance, Epidemiology and End Results (SEER) database as the training cohort, 804 as the internal validation cohort, and 796 patients from the First Affiliated Hospital of Zhengzhou University (n=324) and Jiaxing Maternal and Child Health Hospital (n=472) as the external validation cohort. Least absolute shrinkage and selection operator (LASSO), univariate, and multivariate Cox regression analyses were performed in the training cohort to determine independent prognostic factors for BC, and a nomogram was constructed to predict 3-year, 5-year, and 8-year OS. The final model incorporated 7 factors that significantly affect OS: race, location, positive regional nodes, T stage, N stage, subtype, and grade. The calibration curves showed good consistency between the predicted survival and actual outcomes. Time-dependent receiver operating characteristic (ROC) curves and the time-dependent area under the curve (AUC) confirmed that the accuracy and clinical usefulness of the constructed nomograms were favorable. Decision curve analysis (DCA) and net reclassification improvement (NRI) also demonstrated that this nomogram was more suitable for clinical use than the 7th American Joint Committee on Cancer (AJCC) tumor node metastasis (TNM) staging system and the previous prediction model. In the training cohort and the internal validation cohort, the concordance indices (C-index) of the nomogram for predicting OS (0.723 and 0.649, respectively) were greater than those of the 7th AJCC TNM staging system and the previous prediction model. In addition, based on Kaplan-Meier (K-M) survival curves, the survival differences among different risk stratifications were statistically significant, indicating that our risk model was accurate. In this study, we determined independent prognostic factors for OS in patients with primary nonmetastatic BC treated with chemoradiotherapy and surgery. A new and accurate nomogram for predicting 3-, 5-, and 8-year OS in this patient population was developed and validated for potential clinical applicability.

Unveiling the S=3/2 Kitaev honeycomb spin liquids.

The S=3/2 Kitaev honeycomb model (KHM) is a quantum spin liquid (QSL) state coupled to a static Z2 gauge field. Employing an SO(6) Majorana representation of spin3/2's, we find an exact representation of the conserved plaquette fluxes in terms of static Z2 gauge fields akin to the S=1/2 KHM which enables us to treat the remaining interacting matter fermion sector in a parton mean-field theory. We uncover a ground-state phase diagram consisting of gapped and gapless QSLs. Our parton description is in quantitative agreement with numerical simulations, and is furthermore corroborated by the addition of a [001] single ion anisotropy (SIA) which continuously connects the gapless Dirac QSL of our model with that of the S=1/2 KHM. In the presence of a weak [111] SIA, we discuss an emergent chiral QSL within a perturbation theory.

Unveiling a critical stripy state in the triangular-lattice SU(4) spin-orbital model.

The simplest spin-orbital model can host a nematic spin-orbital liquid state on the triangular lattice. We provide clear evidence that the ground state of the SU(4) Kugel-Khomskii model on the triangular lattice can be well described by a "single" Gutzwiller projected wave function with an emergent parton Fermi surface, despite it exhibits strong finite-size effect in quasi-one-dimensional cylinders. The finite-size effect can be resolved by the fact that the parton Fermi surface consists of open orbits in the reciprocal space. Thereby, a stripy liquid state is expected in the two-dimensional limit, which preserves the SU(4) symmetry while breaks the translational symmetry by doubling the unit cell along one of the lattice vector directions. It is indicative that these stripes are critical and the central charge is c=3, in agreement with the SU(4)1 Wess-Zumino-Witten conformal field theory. All these results are consistent with the Lieb-Schultz-Mattis-Oshikawa-Hastings theorem.

Inhibition of Androgen Receptor Signaling Promotes Prostate Cancer Cell Migration via Upregulation of Annexin A1 Expression.

BACKGROUND: Recent studies indicate that androgen deprivation therapy (ADT), the main therapeutic approach for metastatic prostate cancer (PCa), accelerates PCa invasion and metastasis. Annexin A1 (ANXA1) is a Ca2+-regulated phospholipid-binding protein that can promote PCa migration and invasion. AIM OF THE STUDY: The aim of this study is to determine whether ANXA1 is regulated by ADT and participates in PCa progression after ADT, and to explore the possible mechanism of ANXA1-mediated PCa migration. METHODS: Expression of ANXA1 and androgen receptor (AR) in PCa cell lines and tissues was detected, and the association between these two proteins were analyzed. Expression of ANXA1 was evaluated after AR knockdown or AR inhibition in PCa cell lines. Cell migration of PCa cell liness after ANXA1 knockdown or overexpression was determined by in vitro migration assay. Transcriptome analysis was used to explore the possible mechanism of ANXA1-mediated PCa migration. RESULTS: ANXA1 expression in PCa cell lines and tissues was reversely associated with AR. In vitro studies revealed an increase in ANXA1 expression after AR knockdown or treatment with AR antagonist. Moreover, functional assays indicated that ANXA1 knockdown in PCa cells significantly inhibited cell migration, while ANXA1 overexpression in PCa cells significantly accelerated cell migration. Transcriptome analysis showed that ANXA1 regulated multiple genes involved in cell junction organization, such as CADM1, LIMCH1 and PPM1F. CONCLUSIONS: Our results indicate that ADT might accelerate PCa metastasis via ANXA1 expression and PCa cell migration.

MUC15 inhibits cancer metastasis via PI3K/AKT signaling in renal cell carcinoma.

Patients with renal cell carcinoma (RCC) often develop distant metastasis and the specific molecular mechanism remains poorly understood. In our study, we demonstrated that MUC15, a subtype of mucins family, could suppress the progression of RCC by inhibiting PI3K/AKT signaling. Firstly, we observed that MUC15 was notably decreased in RCC compared to normal tissue. Furthermore, we showed that MUC15 could negatively modulate the migration and invasion of RCC in vitro and in vivo. Mechanistically, we found that knocking-down of MUC15 could active the PI3K/AKT signaling by increasing the AKT phosphorylation and subsequently increase the mRNA and protein expression of MMP2 and MMP9. Interruption of the AKT pathway with the specific inhibitor LY294002 could reverse the expression of MMPs. Therefore, our study clarify the novel function of MUC15 in RCC, which may provide a new sight to diagnose and prevent RCC metastasis.

Distinct Patterns of mRNA and lncRNA Expression Differences Between Lung Squamous Cell Carcinoma and Adenocarcinoma.

This study aimed to assess mRNA and lncRNA expression differences between lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). Cancer tissues were obtained from three LUSC and three LUAD patients, followed by RNA-seq. Differentially expressed mRNAs (DE-mRNAs) and lncRNAs (DE-lncRNAs) were identified between LUSC and LUAD, after which functional enrichment analysis and protein-protein interaction (PPI) network construction was performed on DEGs. Coexpression analysis of lncRNA-gene and prediction of DEG-related miRNAs as well as function enrichment analysis, and construction of competing endogenous RNAs (ceRNA) regulatory network were then conducted. Moreover, survival analysis on differentially expressed RNAs was performed based on data downloaded from The Cancer Genome Atlas (TCGA) database. In this study, 518 DEGs and 117 DE-lncRNAs were identified between LUSC and LUAD. The DEGs were mainly associated with cell adhesion, PI3K-Akt signaling pathway, and focal adhesion. PPI network analysis indicated several genes with highest connectivity, such as CCND1. DE-lncRNAs that coexpressed with DEGs were also associated with tight junction and DE-lncRNAs that had more corepressed relationships with DEGs included GSEC, NKX2-1-AS1, LINC01415, and LINC00839. Moreover, the genes and lncRNAs with higher connectivity in the ceRNA network included NEAT1, SLC5A3, LINC00839, ETV1, CMTM4, and SNX30. Several genes were significantly related to the survival of patients with LUSC and LUAD, including ETV1, RTKN2, SNX30, PAK2, and CCND1. Genes and lncRNAs associated with cell junction have specific patterns in two major histological subtypes of NSCLC. GSEC, NKX2-1-AS1, NEAT1, CCND1, and ETV1 may be potential novel biomarkers for personalized treatment strategies of NSCLC.

STEAP1 facilitates metastasis and epithelial-mesenchymal transition of lung adenocarcinoma via the JAK2/STAT3 signaling pathway.

Six-transmembrane epithelial antigen of prostate-1 (STEAP1) is a relatively newly identified gene target from prostate cancer, breast cancer, and gastric cancer. However, functions of STEAP1 in lung adenocarcinoma (LUAD) are still unknown. In the present study, we explored the molecular and cellular mechanisms of STEAP1 in LUAD. Western blot and Q-PCR were conducted to detect the protein and mRNA expressions respectively. The cell proliferation was tested by CCK8 assay. The effects of STEAP1 on the metastasis and epithelial-mesenchymal transition (EMT) of LUAD were evaluated by EdU assay, wound healing assay, and transwell migratory assay. H1650, H358, HCC827, H1299, H23, A549, H1693 were selected as human LUAD cell lines in the study. Results have shown that STEAP1 expression was up-regulated in LUAD cells compared with normal lung epithelial cells. Knockdowning of STEAP1 suppressed the proliferation, migration, and invasion of LUAD epithelial cells. Importantly, after comparing the proliferation, migration, and invasion of LUAD to the corresponding control groups treated in STAT3 inhibitor ADZ1480, we found that STEAP1 regulates EMT via Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. In conclusion, STEAP1 can serve as a therapeutic target, and it may have important clinical implications for LUAD treatment.

Evidence for nematic superconductivity of topological surface states in PbTaSe2.

Spontaneous symmetry breaking has been a paradigm to describe the phase transitions in condensed matter physics. In addition to the continuous electromagnetic gauge symmetry, an unconventional superconductor can break discrete symmetries simultaneously, such as time reversal and lattice rotational symmetry. In this work we report a characteristic in-plane 2-fold behaviour of the resistive upper critical field and point-contact spectra on the superconducting semimetal PbTaSe2 with topological nodal-rings, despite its hexagonal lattice symmetry (or D3h in bulk while C3v on surface, to be precise). The 2-fold behaviour persists up to its surface upper critical field Hc2R even though bulk superconductivity has been suppressed at its bulk upper critical field Hc2HC≪Hc2R, signaling its probable surface-only electronic nematicity. In addition, we do not observe any lattice rotational symmetry breaking signal from field-angle-dependent specific heat within the resolution. It is worth noting that such surface-only electronic nematicity is in sharp contrast to the observation in the topological superconductor candidate, CuxBi2Se3, where the nematicity occurs in various bulk measurements. In combination with theory, superconducting nematicity is likely to emerge from the topological surface states of PbTaSe2, rather than the proximity effect. The issue of time reversal symmetry breaking is also addressed. Thus, our results on PbTaSe2 shed new light on possible routes to realize nematic superconductivity with nontrivial topology.

KLF4K409Q-mutated meningiomas show enhanced hypoxia signaling and respond to mTORC1 inhibitor treatment.

Meningioma represents the most common primary brain tumor in adults. Recently several non-NF2 mutations in meningioma have been identified and correlated with certain pathological subtypes, locations and clinical observations. Alterations of cellular pathways due to these mutations, however, have largely remained elusive. Here we report that the Krueppel like factor 4 (KLF4)-K409Q mutation in skull base meningiomas triggers a distinct tumor phenotype. Transcriptomic analysis of 17 meningioma samples revealed that KLF4K409Q mutated tumors harbor an upregulation of hypoxia dependent pathways. Detailed in vitro investigation further showed that the KLF4K409Q mutation induces HIF-1α through the reduction of prolyl hydroxylase activity and causes an upregulation of downstream HIF-1α targets. Finally, we demonstrate that KLF4K409Q mutated tumors are susceptible to mTOR inhibition by Temsirolimus. Taken together, our data link the KLF4K409Q mediated upregulation of HIF pathways to the clinical and biological characteristics of these skull base meningiomas possibly opening new therapeutic avenues for this distinct meningioma subtype.

[Effect of ginsenoside Rh2 on transplanted-tumor and expression of JAM in mice].

OBJECTIVE: To discuss the anti-tumor activity of ginsenoside Rh2, we observed the expressions of the junction adhesion molecul (JAM) in transplanted-tumor in mice. METHOD: The models of 40 transplanted-tumor mice that were established by subsequently injecting cancer ascite of mice (S180) with 0.2 mL per mouse into the preepipodite skin were divided into two groups. Experiment group was drenched with 2 mL ginsenoside Rh2 per mouse, equating to a dose 20 mg x kg(-1). Control group was drenched with 2 mL normal saline per mouse. The expression of JAM-1, JAM-2 in the lymphatics, blood vessels and tumours were observed by immunohistochemical staining. RESULT: The expression of JAM-1 on the cancer cells was significantly decreased in experiment group (IA 340.55) as compared with control group (IA 549.90, P<0.05). However, JAM-2 weakly expressed in both two groups. The density of blood vessels in which JAM-1, JAM-2 expressed showed 2.33 and 1.34 in control group, and 1.09 and 0.9 in experiment group respectively. Moreove, the density of lymph vessels were respectively 2.23 and 1.88 in control group compared with 0.99 and 0.79 in experiment group. The expression in blood vessels and lymph vessels in control group were significantly higher than those in experiment group, respectively (P<0.05). CONCLUSION: Ginsenoside Rh2 can affect the tumor growth, further angiogenesis and lymphangiogenesis by down-regulating JAM expression in tumor.

2'­Hydroxyflavanone inhibits epithelial­mesenchymal transition, and cell migration and invasion via suppression of the Wnt/ß­catenin signaling pathway in prostate cancer.

Despite the availability of a number of treatment options, certain cases of primary prostate cancer (PCa) will develop into metastatic PCa, in which epithelial­mesenchymal transition (EMT) serves an important role. Recently, a natural flavonoid known as 2'­hydroxyflavanone (2HF) exerts remarkable anticancer activity on various types of cancer. Our previous study demonstrated that 2HF could promote apoptosis and inhibit the proliferation of PCa cells, but whether 2HF is involved in the regulation of EMT, and cell migration and invasion in metastatic PCa remains unknown. The present study used two different metastatic PCa cell lines (PC­3 and DU145) to investigate the effects of 2HF on EMT, and cell migration and invasion. The results demonstrated that 2HF could inhibit EMT, and cell migration and invasion through the Wnt/ß­catenin signaling pathway by suppressing GSK­3ß phosphorylation, ß­catenin expression and transactivation. In conclusion, the present study revealed a novel function of 2HF, which may be used to prevent or treat PCa metastasis.

Majorana zero modes and long range edge correlation in interacting Kitaev chains: analytic solutions and density-matrix-renormalization-group study.

We study Kitaev model in one-dimension with open boundary condition by using exact analytic methods for non-interacting system at zero chemical potential as well as in the symmetric case of Δ = t, and by using density-matrix-renormalization-group method for interacting system with nearest neighbor repulsion interaction. We suggest and examine an edge correlation function of Majorana fermions to characterize the long range order in the topological superconducting states and study the phase diagram of the interating Kitaev chain.

AKR1C3, a crucial androgenic enzyme in prostate cancer, promotes epithelial-mesenchymal transition and metastasis through activating ERK signaling.

BACKGROUND: AKR1C3, as a crucial androgenic enzyme, facilitates intratumoral androgen biosynthesis and androgen receptor activation in castration-resistant prostate cancer (PCa). The data has shown that AKR1C3 expression is significantly elevated in clinical metastatic PCa specimens, indicating a potential role of AKR1C3 in PCa metastasis. METHODS: C4-2, 22RV1-T, and PC-3 cells with higher AKR1C3 expression were selected and treated with several specific AKR1C3 shRNAs or small molecule inhibitor, and the cell migration and invasion abilities were detected by wound healing assay and Transwell assay. The expression of several epithelial-mesenchymal transition (EMT) markers (i.e., E-cadherin and vimentin) and the related transcription factors (i.e., ZEB1, TWIST1, and SLUG) was examined by Western blot or quantitative PCR assays, and the phosphorylation of AKT or ERK was detected by Western blot. Also, subcutaneous xenografts with 22RV1-T sublines were used to detect in vivo tumor growth, and the expression of E-cadherin, vimentin, and ZEB1 by immunohistochemical staining. The correlation between AKR1C3 and EMT marker expression in clinical specimens was analyzed. RESULTS: AKR1C3 was overexpressed in more aggressive PCa cell lines regardless of the androgen receptor status. Knockdown of AKR1C3 expression or inhibition of AKR1C3 activity could significantly suppress cell migration and invasion abilities in vitro, and increase E-cadherin expression but decrease vimentin expression, in which the phosphorylation of ERK and the EMT-associated transcription factor expression were specifically down-regulated. Also, knockdown of AKR1C3 could suppress PCa tumorigenesis and reverse EMT in vivo. Moreover, there was a significant correlation between AKR1C3 expression and EMT in human PCa specimens from public tissue microarray. CONCLUSIONS: AKR1C3 is a novel EMT driver in PCa metastasis through activating ERK signaling.

The expression and function of RASAL2 in renal cell carcinoma angiogenesis.

Patients with renal cell carcinoma (RCC) often develop resistance to antivascular drugs and eventually succumb to disease. However, the underlying molecular mechanism remains poorly understood. In this study, we demonstrated that RASAL2, a RAS GTPase-activating protein, played a tumor-suppressive role in RCC by targeting tumor angiogenesis. Firstly, we showed that RASAL2 was frequently epigenetically silenced in RCC, and its loss was negatively correlated with overall survival of RCC patients. Furthermore, we discovered that RASAL2 could inhibit RCC angiogenesis in vitro and in vivo. Mechanistically, we identified that RASAL2 could activate GSK3ß by reducing Ser9 phosphorylation and subsequently decrease the expression of c-FOS and vascular endothelial growth factor A (VEGFA). Interruption of the p-GSK3ß/c-FOS pathway with the specific inhibitor or small interfering RNA could reverse the expression of VEGFA, which may provide a new insight to prevent RCC from resistance to antivascular therapy.

RASAL2 inhibits tumor angiogenesis via p-AKT/ETS1 signaling in bladder cancer.

Muscle-invasive or metastatic bladder cancer (BCa) is a life-threatening disease for patients, and tumor angiogenesis is believed to play a critical role in the progression of BCa. However, its underlying mechanism of tumor angiogenesis is still poorly understood. In this study, we discovered that RASAL2, a RAS GTPase activating protein, could inhibit BCa angiogenesis based on our shRNA/siRNA knockdown or ectopic cDNA expression experiments. Mechanistically, RASAL2 downregulation could enhance the phosphorylation of AKT and then subsequently upregulate the expression of ETS1 and VEGFA. Furthermore, there was a negative correlation between RASAL2 and VEGFA or CD31 expression in subcutaneous xenograft and human BCa specimens. Taken together, we provide a new insight into the molecular mechanism of BCa progression, in which RASAL2 can be a new therapeutic target.