Enhanced glucose metabolism mediated by CD147 contributes to immunosuppression in hepatocellular carcinoma.

From a metabolic perspective, cancer may be considered as a metabolic disease characterized by reprogrammed glycolytic metabolism. The aim of the present study was to investigate CD147-mediated glucose metabolic regulation in hepatocellular carcinoma (HCC) and its contribution to altered immune responses in the tumor microenvironment. Several HCC cell lines and corresponding nude mice xenografts models differing in CD147 expressions were established to directly investigate the role of CD147 in the reprogramming of glucose metabolism, and to determine the underlying molecular mechanisms. Immunohistochemistry (IHC) analyses and flow cytometry were used to identify the relationship between reprogrammed glycolysis and immunosuppression in HCC. Upregulated CD147 expressions were found to be associated with enhanced expressions of GLUT1, MCT1 in HCC tumorous tissues. CD147 promoted the glycolytic metabolism in HCC cell lines in vitro via the PI3K/Akt/mTOR signaling pathway. A positive correlation existed between a profile of immunosuppressive lymphocytes infiltration and CD147 expression in HCC tissues. Accumulation of FOXP3-expressing regulatory T cells was induced under a stimulation with lactate in vitro. In conclusion, CD147 promoted glycolytic metabolism in HCC via the PI3K/Akt/mTOR signaling pathway, and was related to immunosuppression in HCC.

CD147-mediated glucose metabolic regulation contributes to the predictive role of 18 F-FDG PET/CT imaging for EGFR-TKI treatment sensitivity in NSCLC.

The aim of this study is to investigate the role of CD147 in glucose metabolic regulation and its association with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment sensitivity prediction using 18 F-fluorodeoxyglucose (18 F-FDG) PET/CT imaging in non-small cell lung cancer (NSCLC). In this study, four human NSCLC cell lines with different EGFR-TKI responses were used to detect p-EGFR/EGFR and CD147 expression via Western blotting and flow cytometric analyses. Radioactive uptake of 18 F-FDG by established stable NSCLC cell lines (HCC827, H1975) with different levels of CD147 expression and the corresponding xenografts was assessed through γ-radioimmunoassays in vitro and micro-PET/CT imaging in vivo to study the role of CD147 in glucose metabolic reprogramming. Correlation analyses were performed to investigate the association between CD147 expression and PD-L1 expression in stable NSCLC cell lines. Higher CD147 expression was found in EGFR-TKI-sensitive NSCLC cell lines than in relatively resistant NSCLC cell lines (HCC827>PC9>A549>H1975). CD147 could promote 18 F-FDG uptake by HCC827 and H1975 cells in vitro and in vivo through an EGFR-initiated Akt/mTOR-dependent signaling pathway. Programmed cell death-ligand 1 (PD-L1) expression was positively correlated with CD147 expression in human NSCLC cell lines. EGFR-TKI treatment sensitivity prediction in NSCLC using 18 F-FDG PET/CT imaging significantly correlated with CD147-mediated glucose metabolic regulation via the Akt/mTOR-dependent pathway. Moreover, PD-L1 expression in NSCLC cell lines could be regulated by CD147, suggesting a potential immunosuppression induced by the upregulation of tumor glucose metabolism.

Reaction Temperature and Partial Pressure Induced Etching of Methylammonium Lead Iodide Perovskite by Trimethylaluminum.

Al2O3 atomic layer deposition (ALD), which uses trimethylaluminum (TMA) as the metal precursor, shows promise in improving the environmental stability of hybrid halide perovskites. However, it is not yet entirely clear how TMA, a strong Lewis acid, reacts with fresh perovskites and how the reaction affects the nucleation of ALD Al2O3. Here, the effects of reaction temperature and partial pressure of TMA on the mechanisms of TMA/CH3NH3PbI3 reactions are investigated. Our real time mass gain data and in situ mass spectrometry data show that the TMA/CH3NH3PbI3 reaction can either remove mass or accumulate mass onto CH3NH3PbI3 substrates, depending strongly on the reaction temperature and partial pressure of TMA. The TMA/CH3NH3PbI3 reaction probably generates TMA-CH3NHx adduct compounds, which protects CH3NH3PbI3 from TMA by forming a shell at 25 °C in the vacuum process. However, these adduct compounds decompose at higher temperatures (e.g., 75 °C). This product layer is much thicker than a monolayer, suggesting the interface formed between Al2O3 coating and CH3NH3PbI3 is blurring and messy. These results have not yet, but should be, carefully considered to correctly interpret the effect of ALD Al2O3 treatment on optoelectronic properties of CH3NH3PbI3.

Reaction between Pyridine and CH3NH3PbI3: Surface-Confined Reaction or Bulk Transformation?

Pyridine molecules have been used to passivate surface Pb2+ sites of CH3NH3PbI3, to recrystallize CH3NH3PbI3, and to bleach CH3NH3PbI3. However, these results contradict each other, as recrystallization and optical-bleach require transformation of bulk CH3NH3PbI3, but surface passivation demands the confinement of the reaction at the surface region. The underlying mechanism for these seemly contradicting results is not yet understood. In this paper, we show, at 25 °C, partial pressure of pyridine vapor is a determining factor for its reaction behaviors with CH3NH3PbI3: one can modify the surface region of CH3NH3PbI3 by using pyridine vapor of pressure 1.15 torr or lower but can transform the whole bulk CH3NH3PbI3 film with a pyridine vapor of 1.3 torr or higher. Our result is the first demonstration that the reaction modes, i.e., surface-confined reaction and bulk transformation, are very sensitive to the partial pressure of under-saturated pyridine vapor. Despite the different reaction behaviors, it is interesting that in all pressure ranges, pyridinium ion is a main product from the reaction between pyridine and CH3NH3PbI3. The bulk transformation is due to the formation of a liquid-like film, which increases the mobility of species to catalyze the reaction between pyridine and CH3NH3PbI3. It is important to note 1.3 torr is much smaller than the saturated vapor pressure of pyridine (20 torr at 25 °C). These findings provide a guidance in applying pyridine and other amines to functionalize and transform CH3NH3PbI3 and other hybrid halide perovskites. It also highlights the critical role of fundamental studies in controllably modifying CH3NH3PbI3.

Probe Decomposition of Methylammonium Lead Iodide Perovskite in N2 and O2 by in Situ Infrared Spectroscopy.

Packaging methylammonium lead iodide perovskite (MAPbI3)-based solar cells with N2 or dry air is a promising solution for its application in outdoor photovoltaics. However, the effect of N2 and O2 on the decomposition chemistry and kinetics of MAPbI3 is not yet well-understood. With in situ Fourier transform infrared spectroscopy measurements, we show that the effective activation energy for the degradation of MAPbI3 in N2 is ∼120 kJ/mol. The decomposition of MAPbI3 is greatly accelerated by exposure to O2 in the dark. As a result of the synergistic effect between O2 and a HeNe laser (633 nm), the degradation rate is further increased with photon flux. This synergistic effect reduces the effective activation energy of degradation of MAPbI3 to ∼50 kJ/mol. The solid decomposition products after annealing in N2 and O2 at 150 °C or below do not have absorbance between 650 and 4000 cm-1.

Application and Indication of Carcinoembryonic Antigen Triggered 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Scanning in the Detection of Relapse of Colorectal Cancer Patients After Curative Therapy.

OBJECTIVE: This study aimed to explore the characteristics of patients with colorectal cancer (CRC) following curative therapy that may benefit from fluorine-18-2-uoro-2-deoxy-D-glucose positron emission tomography/computed tomography (F-FDG PET/CT) scanning, evaluate the application of carcinoembryonic antigen (CEA)-triggered F-FDG PET/CT scanning, and provide referential indicators. METHODS: This retrospective study included 56 CRC patients who received a PET/CT scan as a primary examination because of rising CEA levels after curative therapy and who had not received any other radiological examinations previously. RESULTS: The rate of recurrence or metastasis was 75.0% by PET/CT scan but was 69.6% with follow-up treatment. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 94.9%, 70.6%, 87.5%, 88.1%, and 85.7%, respectively. TNM (tumor, node, metastasis) stage, body mass index, and CEA level were significant prognostic factors. CONCLUSIONS: Positron emission tomography/CT can be selectively applied as a primary examination in CRC patients with asymptomatic elevation of CEA. High CEA levels, increased body mass index, and advanced TNM staging are risk factors for relapse.

A randomized phase II study of autologous cytokine-induced killer cells in treatment of hepatocellular carcinoma.

PURPOSE: This prospective study aims to explore the benefit of cytokine-induced killer cell (CIK) treatment in hepatocellular carcinoma patients, which has not yet been thoroughly studied before. METHODS: From January 2004 to May 2009, 132 patients who were initially diagnosed with hepatocellular carcinoma of Barcelona Clinic Liver Cancer (BCLC) stage A, B or C, Child-Pugh scores of A or B and without prior treatment were enrolled in the study. Patients were randomly assigned to either arm 1 (n = 66) to receive CIK treatment plus standard treatment, or arm 2 (n = 66) to receive standard treatment only. The primary end point was overall survival (OS) and the secondary endpoint was progression-free survival as evaluated by Kaplan-Meier analyses and treatment hazard ratios with the Cox proportional hazards model. RESULTS: The 1-year (OS: 74.2% vs. 50.0%, 95% CI: 63.6-84.8% vs. 37.8-62.2, p = 0.002), 2-year (OS: 53.0% vs. 30.3%, 95% CI: 40.8-65.2% vs. 19.1-41.5%, p = 0.002), 3-year (OS: 42.4% vs. 24.2%, 95% CI: 30.4-54.4% vs. 13.8-34.6%, p = 0.005) and median overall and progression-free survivals of arm 1 patients were significantly higher than those of arm 2. Therefore, in patients who are not suitable for surgery, significant benefit is obtained from CIK treatment. The main adverse effects of CIK included fever, allergy and headache pain. CONCLUSIONS: Hepatocellular carcinoma patients who were not suitable for surgery demonstrate prolonged overall and progression-free survival from CIK treatment.

Synthesis and Structural Optimization of ATG4B Inhibitors for the Attenuation of Autophagy in Glioblastoma.

Glioblastoma, a prevalent malignant CNS tumor, presents a therapeutic challenge because of resistance to standard treatments, including radiation therapy and temozolomide. Both modalities induce autophagy, thereby paradoxically promoting tumor survival. The cysteine protease ATG4B is implicated in this cellular process, which highlights the enzyme as a viable therapeutic target for glioblastoma. We have developed streamlined syntheses for ATG4B inhibitor NSC185058, its derivatives, and fluorogenic ATG4B substrate pim-FG-PABA-AMC. We leveraged these findings to rapidly identify novel compound MJO445, which demonstrates markedly greater potency biochemically and in cells.

RNA splicing analysis deciphers developmental hierarchies and reveals therapeutic targets in adult glioma.

Widespread alterations in RNA alternative splicing (AS) have been identified in adult gliomas. However, their regulatory mechanism, biological significance, and therapeutic potential remain largely elusive. Here, using a computational approach with both bulk and single-cell RNA-Seq, we uncover a prognostic AS signature linked with neural developmental hierarchies. Using advanced iPSC glioma models driven by glioma driver mutations, we show that this AS signature could be enhanced by EGFRvIII and inhibited by in situ IDH1 mutation. Functional validations of 2 isoform switching events in CERS5 and MPZL1 show regulations of sphingolipid metabolism and SHP2 signaling, respectively. Analysis of upstream RNA binding proteins reveals PTBP1 as a key regulator of the AS signature where targeting of PTBP1 suppresses tumor growth and promotes the expression of a neuron marker TUJ1 in glioma stem-like cells. Overall, our data highlights the role of AS in affecting glioma malignancy and heterogeneity and its potential as a therapeutic vulnerability for treating adult gliomas.

Markers of insulin resistance associated with non-alcoholic fatty liver disease in non-diabetic population.

Insulin resistance (IR) plays an important role in the development of non-alcoholic fatty liver disease (NAFLD). IR markers are divided into two types: (1) insulin-based IR marker, homeostatic model assessment of IR (HOMA-IR); and (2) non-insulin-based IR markers, such as triglyceride-glucose (TyG) index, TyG index with body mass index (TyG-BMI), triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-c), and metabolic score for IR (METS-IR). The non-insulin-based IR markers are often associated with lipids. The aim of this study was to analyse the association between IR markers and NAFLD in non-diabetic population. Baseline data of NAFLD and non-NAFLD groups were compared. Logistic regression was used to evaluate the relationship between five IR markers and NAFLD risk. The odds ratios (ORs) and 95% confidence intervals (CIs) of IR markers were calculated. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to evaluate the ability of different IR markers to detect NAFLD. Subgroup analyses were performed in obese and non-obese subgroups. This study found a positive correlation between NAFLD risk and elevation in five IR markers (HOMA-IR, TyG, TyG-BMI, TG/HDL-c, and METS-IR). In non-obese subjects, the AUC of TyG-BMI was larger than that of the other four IR markers to detect NAFLD. The AUC of HOMA-IR was larger than that of the other four IR markers to detect NAFLD in obese subjects. In non-diabetic population, the five IR markers are associated with the risk of NAFLD, including non-obese and obese NAFLD. TyG-BMI and HOMA-IR can be used to detect non-obese and obese NAFLD, respectively, with better detection ability compared with the other IR markers.

HOMA-IR is an effective biomarker of non-alcoholic fatty liver disease in non-diabetic population.

OBJECTIVES: This study aimed to investigate the correlation between homeostasis model assessment of insulin resistance (HOMA-IR) and non-alcoholic fatty liver disease (NAFLD) in the non-diabetic population and establish its diagnostic efficacy. METHODS: This observational study involved participants divided into NAFLD and non-NAFLD groups, and baseline data were analyzed. Univariate and multivariate logistic regression analyses were used to correlate HOMA-IR with the risk of NAFLD. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of HOMA-IR for NAFLD. Subgroup analyses of non-obese individuals were performed. RESULTS: Overall, 2234 non-diabetic participants were included. The HOMA-IR was significantly higher in the NAFLD group than in the non-NAFLD group. Multivariate logistic regression analysis showed that HOMA-IR was a strong and independent risk factor for NAFLD after correcting for confounding factors. The area under the ROC curve (AUC) value of HOMA-IR for predicting NAFLD was 0.792. In the non-obese non-diabetic population, HOMA-IR was an independent risk factor for increased risk of lean NAFLD after correcting for confounding factors. The AUC value of HOMA-IR for predicting lean NAFLD was 0.770. CONCLUSIONS: HOMA-IR is independently associated with the risk of NAFLD in the non-diabetic and non-obese non-diabetic populations and has good diagnostic value.

CD73, a Promising Therapeutic Target of Diclofenac, Promotes Metastasis of Pancreatic Cancer through a Nucleotidase Independent Mechanism.

CD73, a cell surface-bound nucleotidase, facilitates extracellular adenosine formation by hydrolyzing 5'-AMP to adenosine. Several studies have shown that CD73 plays an essential role in immune escape, cell proliferation and tumor angiogenesis, making it an attractive target for cancer therapies. However, there are limited clinical benefits associated with the mainstream enzymatic inhibitors of CD73, suggesting that the mechanism underlying the role of CD73 in tumor progression is more complex than anticipated, and further investigation is necessary. In this study, CD73 is found to overexpress in the cytoplasm of pancreatic ductal adenocarcinoma (PDAC) cells and promotes metastasis in a nucleotidase-independent manner, which cannot be restrained by the CD73 monoclonal antibodies or small-molecule enzymatic inhibitors. Furthermore, CD73 promotes the metastasis of PDAC by binding to the E3 ligase TRIM21, competing with the Snail for its binding site. Additionally, a CD73 transcriptional inhibitor, diclofenac, a non-steroidal anti-inflammatory drug, is more effective than the CD73 blocking antibody for the treatment of PDAC metastasis. Diclofenac also enhances the therapeutic efficacy of gemcitabine in the spontaneous KPC (LSL-KrasG12D/+ , LSL-Trp53R172H/+ , and Pdx-1-Cre) pancreatic cancer model. Therefore, diclofenac may be an effective anti-CD73 therapy, when used alone or in combination with gemcitabine-based chemotherapy regimen, for metastatic PDAC.

Interaction between regulatory T cells and cancer stem cells.

The concept that cancer stem cells (CSCs)/tumor stem cells/cancer-initiating cells are one of the key centers to cure neoplastic disease has drawn an increasing attention recent years. Because of their high resistance and potential to initiate tumors, CSCs are considered a critical factor associated with tumor relapse. Regulatory T(T(reg)) cells, a group of immune cells with tumor-promoting effect, exert their function through inhibition of effector T cells and regulation of the tumor microenvironment by producing a series of soluble factors. However, the interactions between T(reg)s and CSCs are less understood. The mechanisms of how T(reg)s, as tumor-promoting cells, manipulate CSCs remain obscure. In this review, we elucidate their interactions.

Signaling cascades initiated by TSLP-mediated signals in different cell types.

Thymic stromal lymphopoietin (TSLP) has been well characterized as a consequence of its ability to modulate allergic and neoplastic diseases. However, downstream signaling mediated by TSLP varies significantly between the cell type and species examined. Since this observation is often overlooked and in some cases ignored, this review aims to consolidate the molecular pathways activated by TSLP receptors expressed by various human and mouse cell types.

The Predictive Role of Immune Related Subgroup Classification in Immune Checkpoint Blockade Therapy for Lung Adenocarcinoma.

Background: In lung adenocarcinoma (LUAD), the predictive role of immune-related subgroup classification in immune checkpoint blockade (ICB) therapy remains largely incomplete. Methods: Transcriptomics analysis was performed to evaluate the association between immune landscape and ICB therapy in lung adenocarcinoma and the associated underlying mechanism. First, the least absolute shrinkage and selection operator (LASSO) algorithm and K-means algorithm were used to identify immune related subgroups for LUAD cohort from the Cancer Genome Atlas (TCGA) database (n = 572). Second, the immune associated signatures of the identified subgroups were characterized by evaluating the status of immune checkpoint associated genes and the immune cell infiltration. Then, potential responses to ICB therapy based on the aforementioned immune related subgroup classification were evaluated via tumor immune dysfunction and exclusion (TIDE) algorithm analysis, and survival analysis and further Cox proportional hazards regression analysis were also performed for LUAD. In the end, gene set enrichment analysis (GSEA) was performed to explore the metabolic mechanism potentially responsible for immune related subgroup clustering. Additionally, two LUAD cohorts from the Gene Expression Omnibus (GEO) database were used as validation cohort. Results: A total of three immune related subgroups with different immune-associated signatures were identified for LUAD. Among them, subgroup 1 with higher infiltration scores for effector immune cells and immune checkpoint associated genes exhibited a potential response to IBC therapy and a better survival, whereas subgroup 3 with lower scores for immune checkpoint associated genes but higher infiltration scores for suppressive immune cells tended to be insensitive to ICB therapy and have an unfavorable prognosis. GSEA revealed that the status of glucometabolic reprogramming in LUAD was potentially responsible for the immune-related subgroup classification. Conclusion: In summary, immune related subgroup clustering based on distinct immune associated signatures will enable us to screen potentially responsive LUAD patients for ICB therapy before treatment, and the discovery of metabolism associated mechanism is beneficial to comprehensive therapeutic strategies making involving ICB therapy in combination with metabolism intervention for LUAD.

Identification of Ferroptosis-Related Genes Signature Predicting the Efficiency of Invasion and Metastasis Ability in Colon Adenocarcinoma.

Background: Colon adenocarcinoma (COAD) is one of the most prevalent cancers worldwide and has become a leading cause of cancer death. Although many potential biomarkers of COAD have been screened with the bioinformatics method, it is necessary to explore novel markers for the diagnosis and appropriate individual treatments for COAD patients due to the high heterogeneity of this disease. Epithelial-to-mesenchymal transition (EMT)-mediated tumor metastasis suggests poor prognosis of cancers. Ferroptosis is involved in tumor development. EMT signaling can increase the cellular sensitivity to ferroptosis in tumors. The aim of our study is finding novel prognostic biomarkers to determine COAD patients for predicting efficiency of metastasis status and targeting precise ferroptosis-related therapy. Methods: A novel gene signature related to metastasis and ferroptosis was identified combing with risk model and WGCNA analysis with R software. The biological functions and predictive ability of the signature in COAD were explored through bioinformatics analysis. Results: We established a four-gene prognostic signature (MMP7, YAP1, PCOLCE, and HOXC11) based on EMT and ferroptosis related genes and validated the reliability and effectiveness of this model in COAD. This four-gene prognostic signature was closely connected with metastasis and ferroptosis sensitivity of COAD. Moreover, WGCNA analysis further confirmed the correlation between PCOLCE, HOXC11, and liver and lymphatic invasion of COAD. Conclusion: The four genes may become potential prognostic biomarkers to identify COAD patients with metastasis. Moreover, this four-gene signature may be able to determine the COAD suitable with ferroptosis induction therapy. Finally, PCOLCE2 and HOXC11 were selected individually because of their novelties and precise prediction ability. Overall, this signature provided novel possibilities for better prognostic evaluation of COAD patients and may be of great guiding significance for individualized treatment and clinical decision.

CD73 induces gemcitabine resistance in pancreatic ductal adenocarcinoma: A promising target with non-canonical mechanisms.

CD73, a cell surface-localized ecto-5'-nucleotidase, is the major enzymatic source of extracellular adenosine. Canonically, it plays multiple roles in cancer-related processes via its metabolite. As a druggable target, clinical trials targeting CD73 in various malignant diseases are currently ongoing. Here, we report the ecto-5'-nucleotidase-independent functions of CD73 in pancreatic ductal adenocarcinoma (PDAC). Our findings support that the elevated expression of CD73 in PDAC cells promotes gemcitabine (GEM) resistance by activating AKT. We discovered that a large amount of intracellular CD73 are localized in the endoplasmic reticulum membrane. Intracellular CD73 physically interacts with major vault protein to activate the SRC-AKT circuit. Troglitazone (TGZ) is a peroxisome proliferator-activated receptor gamma agonist that could inhibit the expression of CD73. The administration of TGZ markedly enhances sensitivity to GEM via downregulating CD73 in PDAC. Our findings support that CD73 could be targeted to overcome chemoresistance in PDAC.

Stable and Catalytically Active Shape-Engineered Cerium Oxide Nanorods by Controlled Doping of Aluminum Cations.

Shape-engineered nanocrystals (SENs) promise a better selectivity and a higher activity in catalytic reactions than the corresponding non-shape-engineered ones because of their larger specific surface areas and desirable crystal facets. However, often, it is challenging to apply SENs in practical catalytic applications at high reaction temperatures, where SENs deforms into more stable, less active nanoparticles. In this paper, we show that atomic layer deposition (ALD) of Al2O3 at 200 °C can controllably dope Al cations into the shape-engineered CeO2 nanorods (NRs) to not only increase their shape transition temperature from 400 °C to beyond 700 °C but also greatly increase their specific reversible oxygen storage capacity (srOSC). The substituted Al3+ ions impede the surface diffusion of Ce ions and therefore improve the thermal stability of CeO2 NRs. These Al3+ dopants form -Al-O-Ce-O- clusters, which are new Ce species and can be reversibly reduced and oxidized at 500-700 °C. This low-temperature chemical doping method decouples the synthesis process of SENs from the doping process and maintains the shape of the SENs during the activation of dopants. This concept could be adopted to enable the applications of other SENs in challenging high-temperature environments.

Enhanced glucose metabolism mediated by CD147 is associated with 18 F-FDG PET/CT imaging in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most deadly thoracic tumors. Reprogrammed glycolytic metabolism is a hallmark of cancer cells and significantly affects several cellular functions. In the current study, we aimed to investigate cluster of differentiation 147 (CD147)-mediated glucose metabolic regulation in LUAD and its association with 18 F-FDG PET/CT imaging. METHODS: The expression profile and prognostic potential of CD147 in LUAD were analyzed using UALCAN and a Kaplan-Meier plotter. Tissue immunohistochemical analyses and PET metabolic parameters were used to identify the relationship between CD147 expression and reprogrammed glycolysis. The role of CD147 in glucose metabolic reprogramming was assessed by radioactive uptake of 18 F-FDG through γ-radioimmunoassays in vitro and micro-PET/CT imaging in vivo. Western blotting assays were used to determine the expression level of monocarboxylate transporter 1 (MCT1) and MCT4 in established human LUAD cell lines (ie, HCC827 and H1975) with different CD147 expression levels via lentiviral transduction. RESULTS: CD147 was highly expressed in LUAD. A significant positive correlation existed between CD147 expression and PET metabolic parameters(SUVmax,SUVmean, SUVpeak). CD147 could promote radioactive uptake of 18 F-FDG in vitro and in vivo, suggesting the ability of CD147 to enhance glycolytic metabolism. Furthermore, as an obligate chaperone for MCT1 and MCT4, CD147 positively correlated with MCT1 and MCT4 expression in LUAD tissues and established cell lines with different CD147 expression. CONCLUSIONS: Our study revealed that CD147 is a promising novel target for LUAD treatment and CD147-mediated glucose metabolism demonstrated its contribution to the predictive role of 18 F-FDG PET/CT imaging for targeted therapeutic efficacy.

MicroRNA-520c-3p functions as a novel tumor suppressor in lung adenocarcinoma.

Lung cancer is a malignancy with one of the highest incidence rates, and it is the leading cause of cancer-related death. To gain further insights into the underlying mechanisms of tumor growth and metastasis, we investigated the role and expression of microRNAs in lung adenocarcinoma (LUAD). We discovered a significantly lower expression level of microRNA-520c-3p (miR-520c-3p) in LUAD tissues than in nontumor tissues. miR-520c-3p is known to regulate multiple biological functions and cellular behaviors. In this study, we show that AKT1 and AKT2 are key direct targets of miR-520c-3p, which are required for its biological roles in LUAD. Mechanistically, downregulation of miR-520c-3p in LUAD is due to DNA methylation of the miR-520c-3p promoter region. Conversely, the activity of the transcription factor Yin Yang 1 (YY1) results in the upregulation of miR-520c-3p. Taken together, our results reveal methylation/YY1/miR-520c-3p/AKT1/AKT2 as a molecular axis with a potent biological function and highlight miR-520c-3p as a novel potent tumor suppressor in LUAD.