Exploration of the prognostic prediction value of the PANoptosis-based risk score and its correlation with tumor immunity in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a common cancer with high mortality worldwide. PANoptosis is a novel inflammatory programmed cell death modality with the characteristics of pyroptosis, apoptosis and necroptosis. It is necessary to explore PANoptosis-related genes in LUAD patients and offer evidence for prognosis prediction and therapeutic strategies. Single-cell RNA sequencing data and RNA expression profiles of LUAD patients from The Cancer Genome Atlas and Gene Expression Omnibus databases are used to screen PANoptosis-related differential genes for the construction of a risk model. Fifteen PANoptosis-related markers with prognostic value were identified by Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression analysis. Kaplan-Meier analysis and receiver operating characteristic curve analysis further demonstrated the significant predictive capability. Immune infiltration, Single Nucleotide Variants (SNV) mutations, and clinical drug susceptibility were analyzed. In conclusion, a risk model of 15 PANoptosis-related genes has significant value in prognostic prediction for LUAD and has potential to direct clinical therapeutic strategies during the treatment.

FSTL3 is associated with prognosis and immune cell infiltration in lung adenocarcinoma.

PURPOSE: FSTL3 expression is altered in various types of cancer. However, the role and mechanism of action of FSTL3 in lung adenocarcinoma development and tumor immunity are unknown. We investigated the association between FSTL3 expression and clinical characteristics and immune cell infiltration in lung adenocarcinoma samples from The Cancer Genome Atlas (TCGA) and a separate validation set from our hospital. METHODS: Data on immune system infiltration, gene expression, and relevant clinical information were obtained by analyzing lung adenocarcinoma sample data from TCGA database. Using online tools like GEPIA, the correlations between FSTL3 expression and prognosis, clinical stage, survival status, and tumor-infiltrating immune cells were examined. In a validation dataset, immunohistochemistry was performed to analyze FSTL3 expression and its related clinical characteristics. RESULTS: FSTL3 expression was markedly reduced in patients with lung adenocarcinoma. N stage, pathological stage, and overall survival were significantly correlated with FSTL3 expression. According to GSEA, FSTL3 is strongly linked to signaling pathways such as DNA replication and those involved in cell cycle regulation. Examination of TCGA database and TIMER online revealed a correlation between FSTL3 and B cell, T cell, NK cell, and neutrophil levels. The prognosis of patients with lung adenocarcinoma was significantly affected by six genes (KRT6A, VEGFC, KRT14, KRT17, SNORA12, and KRT81) related to FSTL3. CONCLUSION: FSTL3 is significantly associated with the prognosis and progression of lung adenocarcinoma and the infiltration of immune cells. Thus, targeting FSTL3 and its associated genes in immunotherapy could be potentially beneficial for the treatment of lung adenocarcinoma.

Value of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration to Diagnose the Lung Nodules Related Enlarged Mediastinal Lymph Nodes.

Background: To investigate the value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of lung nodules related enlarged mediastinal lymph nodes (MLNs). Methods: Clinical data of 108 patients with lung nodules related enlarged MLNs who underwent EBUS-TBNA in our single center were retrospectively analyzed from January 2020 to December 2021. The sensitivity and specificity of EBUS-TBNA in malignancy diagnosis were evaluated. Associations between ultrasonic image measurement indexes and malignancy diagnosis were explored. The receiver operating characteristic (ROC) curve of these indexes, the area under curve (AUC), and the corresponding cut-off values were calculated to predict malignant MLNs. Results: Sensitivity, specificity, and accuracy of EBUS-TBNA in the diagnosis of lung nodules related malignant MLNs were 89.47%, 100%, and 92.59%, respectively. There were significantly higher proportions of malignant MLNs with clear boundary, short diameter ≥1 cm, lower long to short diameter ratio, abundant flow of blood, and destructed medulla than that of benign ones (P < .05). According to ROC curve analysis, the cut-off value of short diameters for predicting malignant MLNs was 1.085 cm, and the AUC was 0.796 (95% confidence interval: 0.724-0.868, P < .001). Corresponding sensitivity and specificity were 61.36% and 80.00%, respectively. The cut-off value of the long to short diameter ratio for predicting malignancy was 1.405, and the AUC was 0.697 (95% confidence interval: 0.609-0.790, P < .001). Corresponding sensitivity and specificity were 70.00% and 71.97%, respectively. Conclusion: EBUS-TBNA has a satisfactory accuracy of lung nodules related MLNs diagnosis. Short diameters and long to short diameter ratio of lung nodules related MLNs in ultrasonic image may contribute to the prediction of malignant lymph nodes.

Natural glycosidic antioxidants from Cynanchum atratum roots.

Two new rhamnosides, 18-O-α-l-rhamnopyranosylabietic acid (1) and (E)-3,5-dimethoxystilben-4'-O-α-l-rhamnopyranoside (2), five known glucosides (3-7) along with three others were isolated from Cynanchum atratum roots. The structures of new compounds were elucidated by physical data analyses such as NMR, UV, IR, HR-ESI-MS, as well as acid hydrolysis. All of them were assessed for their antioxidant activities through 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical ion (ABTS•+), 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH•) and 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO•) assay, with l-ascorbic acid used as the positive control. As a result, compounds 3-5 exhibited obvious antioxidant activities. These bioactive components could be promising antioxidants.

LncRNA FENDRR Servers as a Possible Marker of Essential Hypertension and Regulates Human Umbilical Vein Endothelial Cells Dysfunction via miR-423-5p/Nox4 Axis.

Purpose: Essential hypertension (EH) is an intricate non-communicable infirmity and lncRNAs are validated as essential mediators in EH. The study aimed to propose the expression pattern of FENDRR and miR-423-5p, substantiate the potential mechanism of FENDRR/miR-423-5p/Nox4 axis in EH. Patients and Methods: The expression of FENDRR and miR-423-5p was evaluated by qRT-PCR and the clinical significance was explored by the ROC curve. Pearson correlation indicated the relationship between FENDRR and miR-423-5p. The function of FENDRR and miR-423-5p on HUVECs was clarified by CCK-8 assay, Transwell assay, and flow cytometry. Western blot was used to assess the relative protein expression of Nox4. Results: FENDRR was highly expressed and miR-423-5p was lowly expressed in EH patients and a negative correlation between them was determined. FENDRR might serve as a predictive diagnosis in differentiating EH patients. Knockdown of FENDRR or overexpression of miR-423-5p showed expansionary effects in cell proliferation, cell migration, and inhibiting cell apoptosis. Meanwhile, miR-423-5p was determined as a target of FENDRR and mediated the function of FENDRR on HUVECs. Moreover, Nox4 is a down-streaming target gene of miR-423-5p. The protein expression of Nox4 was regulated by the alternation of miR-423-5p expression. Conclusion: FENDRR played an energetic role in EH and contributed to HUVECs dysfunction by restricting cell proliferation, suppressing cell migration, and accelerating cell apoptosis by manipulating the miR-423-5p/Nox4 axis.

Circ-ATIC Serves as a Sponge of miR-326 to Accelerate Esophageal Squamous Cell Carcinoma Progression by Targeting ID1.

In the previous studies, circular RNA (circRNA) has been shown to be closely related to the occurrence and development of various cancers. However, the role and mechanism of circ-ATIC in the progression of esophageal squamous cell carcinoma (ESCC) is not yet clear. Quantitative real-time PCR was used to detect the expression levels of circ-ATIC, microRNA (miR)-326 and inhibitor of DNA binding 1 (ID1) in tissues (n = 50) and cells. Cell counting kit 8 assay, colony formation assay, flow cytometry, wound-healing assay and transwell assay were performed to measure the proliferation, apoptosis, migration, and invasion of cells. In addition, the oxidative stress of cells was evaluated by detecting the productions of superoxide dismutase and malondialdehyde. Animal studies were implied to explore the role of circ-ATIC in ESCC tumor growth. The relationship between circ-ATIC and miR-326 or ID1 was determined by dual-luciferase reporter assay and RNA immunoprecipitation assay. Additionally, the protein expression of ID1 was examined by western blot assay. Circ-ATIC was found to be upregulated in ESCC tissues and cells. Silenced circ-ATIC suppressed the proliferation, migration, invasion, promoted the apoptosis and oxidative stress of ESCC cells. The tumor growth of ESCC also was inhibited by circ-ATIC knockdown. Furthermore, we found that circ-ATIC could sponge miR-326, and miR-326 could target ID1. The rescue experiments revealed that miR-326 inhibitor could reverse the negative regulation of circ-ATIC silencing on ESCC progression, and ID1 overexpression also inverted the inhibitory effect of miR-326 on ESCC progression. In addition, we confirmed that the expression of ID1 was positively regulated by circ-ATIC. Our study showed that circ-ATIC facilitated the progression of ESCC by regulating the miR-326/ID1 axis, indicating that circ-ATIC might be a target for ESCC treatment.

MiR-519d-3p enhances the sensitivity of non-small-cell lung cancer to tyrosine kinase inhibitors.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. Tyrosine kinase inhibitors (TKIs) are currently the most effective chemotherapy for NSCLC. However, most cancer patients develop TKI resistance at tumor relapse stage. We firstly measured the expression change of miR-519d-3p in TKI resistance NSCLC cells. We then ectopically expressed miR-519-3p in TKI resistant cells to study its functional impact on cell proliferation, migration, invasion and cell sensitivity to gefitinib. The downstream target of miR-519-3p was identified by bioinformatics and validated in luciferase reporter assay and western blotting analysis. We also studied the reversing effect of the candidate target in NSCLC cells expressing miR-519d-3p. Lastly, we compared the miR-519d-3p level in NSCLC patients with good or poor response to gefitinib. miR-519d-3p level was downregulated in TKI resistant NSCLC cells. The restoration of miR-519d-3p in these NSCLC cells inhibited cell proliferation, invasion and migration; enhanced cell sensitivity to gefitinib. EPAS1 was identified and validated as downstream target of miR-519d-3p. Co-expressing EPAS1 antagonized the inhibitory effect of miR-519d-3p on NSCLC cells. MiR-519d-3p was downregulated in NSCLC patients with poor response to gefitinib. Targeting miR-519d-3p/EPAS1 axis may provide alternative treatment for TKI-resistant NSCLC.

Resveratrol Ameliorates High-Fat-Diet-Induced Abnormalities in Hepatic Glucose Metabolism in Mice via the AMP-Activated Protein Kinase Pathway.

Diabetes mellitus is highly prevalent worldwide. High-fat-diet (HFD) consumption can lead to liver fat accumulation, impair hepatic glycometabolism, and cause insulin resistance and the development of diabetes. Resveratrol has been shown to improve the blood glucose concentration of diabetic mice, but its effect on the abnormal hepatic glycometabolism induced by HFD-feeding and the mechanism involved are unknown. In this study, we determined the effects of resveratrol on the insulin resistance of high-fat-diet-fed mice and a hepatocyte model by measuring serum biochemical indexes, key indicators of glycometabolism, glucose uptake, and glycogen synthesis in hepatocytes. We found that resveratrol treatment significantly ameliorated the HFD-induced abnormalities in glucose metabolism in mice, increased glucose absorption and glycogen synthesis, downregulated protein phosphatase 2A (PP2A) and activated Ca2+/CaM-dependent protein kinase kinase ß (CaMKKß), and increased the phosphorylation of AMP-activated protein kinase (AMPK). In insulin-resistant HepG2 cells, the administration of a PP2A activator or CaMKKß inhibitor attenuated the effects of resveratrol, but the administration of an AMPK inhibitor abolished the effects of resveratrol. Resveratrol significantly ameliorates abnormalities in glycometabolism induced by HFD-feeding and increases glucose uptake and glycogen synthesis in hepatocytes. These effects are mediated through the activation of AMPK by PP2A and CaMKKß.

EPAS1 promotes peritoneal carcinomatosis of non-small-cell lung cancer by enhancing mesothelial-mesenchymal transition.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is a major cause of cancer-related death globally. Endothelial PAS domain-containing protein 1 (EPAS1) is a homolog of the hypoxia-inducible factor 1α and has been reported to confer tyrosine kinase inhibitor (TKI) resistance in NSCLC, but its role in peritoneal carcinomatosis of NSCLC is unknown. METHODS: PC14HM, a high metastatic potential subline of NSCLC cell line PC14, was derived. Stable shRNA knockdown of EPAS1 was then established in PC14HM cells and subjected to assessment regarding the effects on proliferation and viability, xenograft tumor growth, metastatic potential, mesothelial-mesenchymal transition (MMT)-related characteristics and peritoneal carcinomatosis in a mouse model. RESULTS: EPAS1 expression was elevated in PC14HM cells. Knockdown of EPAS1 inhibited the proliferation and viability of PC14HM cells in vitro and suppressed tumorigenesis in vivo. In addition, the metastatic features and in vitro productions of MMT-inducing factors in PC14HM cells was also associated with EPAS1. More importantly, knockdown of EPAS1 drastically suppressed peritoneal carcinomatosis of PC14HM cells in vivo. CONCLUSION: EPAS1 promotes peritoneal carcinomatosis of NSCLC through enhancement of MMT and could therefore serve as a prognostic marker or a therapeutic target in treating NSCLC, particularly in patients with peritoneal carcinomatosis.

Pyruvate Kinase Controls Signal Strength in the Insulin Secretory Pathway.

Pancreatic ß cells couple nutrient metabolism with appropriate insulin secretion. Here, we show that pyruvate kinase (PK), which converts ADP and phosphoenolpyruvate (PEP) into ATP and pyruvate, underlies ß cell sensing of both glycolytic and mitochondrial fuels. Plasma membrane-localized PK is sufficient to close KATP channels and initiate calcium influx. Small-molecule PK activators increase the frequency of ATP/ADP and calcium oscillations and potently amplify insulin secretion. PK restricts respiration by cyclically depriving mitochondria of ADP, which accelerates PEP cycling until membrane depolarization restores ADP and oxidative phosphorylation. Our findings support a compartmentalized model of ß cell metabolism in which PK locally generates the ATP/ADP required for insulin secretion. Oscillatory PK activity allows mitochondria to perform synthetic and oxidative functions without any net impact on glucose oxidation. These findings suggest a potential therapeutic route for diabetes based on PK activation that would not be predicted by the current consensus single-state model of ß cell function.

Multi-Tissue Acceleration of the Mitochondrial Phosphoenolpyruvate Cycle Improves Whole-Body Metabolic Health.

The mitochondrial GTP (mtGTP)-dependent phosphoenolpyruvate (PEP) cycle couples mitochondrial PEPCK (PCK2) to pyruvate kinase (PK) in the liver and pancreatic islets to regulate glucose homeostasis. Here, small molecule PK activators accelerated the PEP cycle to improve islet function, as well as metabolic homeostasis, in preclinical rodent models of diabetes. In contrast, treatment with a PK activator did not improve insulin secretion in pck2-/- mice. Unlike other clinical secretagogues, PK activation enhanced insulin secretion but also had higher insulin content and markers of differentiation. In addition to improving insulin secretion, acute PK activation short-circuited gluconeogenesis to reduce endogenous glucose production while accelerating red blood cell glucose turnover. Four-week delivery of a PK activator in vivo remodeled PK phosphorylation, reduced liver fat, and improved hepatic and peripheral insulin sensitivity in HFD-fed rats. These data provide a preclinical rationale for PK activation to accelerate the PEP cycle to improve metabolic homeostasis and insulin sensitivity.

Endocrine-Exocrine Signaling Drives Obesity-Associated Pancreatic Ductal Adenocarcinoma.

Obesity is a major modifiable risk factor for pancreatic ductal adenocarcinoma (PDAC), yet how and when obesity contributes to PDAC progression is not well understood. Leveraging an autochthonous mouse model, we demonstrate a causal and reversible role for obesity in early PDAC progression, showing that obesity markedly enhances tumorigenesis, while genetic or dietary induction of weight loss intercepts cancer development. Molecular analyses of human and murine samples define microenvironmental consequences of obesity that foster tumorigenesis rather than new driver gene mutations, including significant pancreatic islet cell adaptation in obesity-associated tumors. Specifically, we identify aberrant beta cell expression of the peptide hormone cholecystokinin (Cck) in response to obesity and show that islet Cck promotes oncogenic Kras-driven pancreatic ductal tumorigenesis. Our studies argue that PDAC progression is driven by local obesity-associated changes in the tumor microenvironment and implicate endocrine-exocrine signaling beyond insulin in PDAC development.

Mitochondrial GTP Links Nutrient Sensing to ß Cell Health, Mitochondrial Morphology, and Insulin Secretion Independent of OxPhos.

Mechanisms coordinating pancreatic ß cell metabolism with insulin secretion are essential for glucose homeostasis. One key mechanism of ß cell nutrient sensing uses the mitochondrial GTP (mtGTP) cycle. In this cycle, mtGTP synthesized by succinyl-CoA synthetase (SCS) is hydrolyzed via mitochondrial PEPCK (PEPCK-M) to make phosphoenolpyruvate, a high-energy metabolite that integrates TCA cycling and anaplerosis with glucose-stimulated insulin secretion (GSIS). Several strategies, including xenotopic overexpression of yeast mitochondrial GTP/GDP exchanger (GGC1) and human ATP and GTP-specific SCS isoforms, demonstrated the importance of the mtGTP cycle. These studies confirmed that mtGTP triggers and amplifies normal GSIS and rescues defects in GSIS both in vitro and in vivo. Increased mtGTP synthesis enhanced calcium oscillations during GSIS. mtGTP also augmented mitochondrial mass, increased insulin granule number, and membrane proximity without triggering de-differentiation or metabolic fragility. These data highlight the importance of the mtGTP signal in nutrient sensing, insulin secretion, mitochondrial maintenance, and ß cell health.

Characterization, Antimicrobial Properties and Coatings Application of Gellan Gum Oxidized with Hydrogen Peroxide.

The effect of hydrogen peroxide (H2O2) oxidation on the physicochemical, gelation and antimicrobial properties of gellan gum was studied. The oxidized gellan gum (OGG) was characterized by measuring the carboxyl/carbonyl group contents, Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (¹H-NMR) spectroscopy. The H2O2 oxidation resulted in a large increase in the carboxyl groups in gellan gum. The OGG lost gelation ability by oxidation even in the presence of metal ions. The antimicrobial activities of the OGG against Gram-positive bacteria (Staphylococcus aureus), Gram-negative bacteria (Escherichia coli), and fungal (Aspergillus niger) were tested. The OGG could inhibit the growth of both bacteria and fungal, and the activity was improved with an increase in the oxidation level. Finally, the application of the OGG as an active coatings material to extend the storage of apples was tested.

SGLT2 knockout prevents hyperglycemia and is associated with reduced pancreatic ß-cell death in genetically obese mice.

Inhibition of the sodium-glucose co-transporter type 2 (SGLT2) has received growing acceptance as a novel, safe and effective means to improve glycemic control in patients with type 2 diabetes. Inhibition of SGLT2 lowers the renal glucose threshold and reduces plasma glucose by promoting glucose excretion in urine. Both animal studies and clinical trials in man suggest that SGLT2 inhibition has the potential to improve pancreatic ß-cell function by reducing glucose toxicity. However, there is limited data exploring how reducing glucotoxicity via SGLT2 inhibition affects rates of ß-cell proliferation and death throughout life in the context of insulin resistance and type 2 diabetes. SGLT2-/- mice were backcrossed to the db/db strain to produce littermate control db/db-SGLT2+/+ and experimental db/db-SGLT2-/- mice. Mice were euthanized at 5, 12 and 20 weeks of age to collect plasma for glucose, insulin, lipid and cytokine measures, and pancreata for histological analysis including determination of ß-cell mass and rates of proliferation and death. SGLT2 deletion in db/db mice reduced plasma glucose as early as 5 weeks of age and continued throughout life without changes in plasma lipids or cytokines. Reduced plasma glucose levels occurred in parallel with an increase in the relative ß-cell volume and reduced frequency of ß-cell death, and no apparent change in rates of ß-cell proliferation. These data add to a growing body of evidence demonstrating that improved glycemic control achieved through SGLT2 inhibition can preserve ß-cell function and endogenous insulin secretion by reducing glucose toxicity and rates of ß-cell death.

LncRNA DANCR Promotes Lung Cancer by Sequestering miR-216a.

BACKGROUND: Long noncoding RNAs (lncRNAs) are a new class of cancer regulators. Here, we aimed to investigate the diagnostic and therapeutic values of an lncRNA, differentiation antagonizing noncoding RNA (DANCR), in lung cancer. METHODS: Real-time polymerase chain reaction was used to compare DANCR levels in normal and cancerous lung tissues as well as lung cancer cells. Lentiviral transduction was used to induce DANCR overexpression or silencing in vitro, followed by monitoring cell proliferation, colony formation, and changes in microRNA-216a (miR-216a) expression. DANCR-specific small hairpin RNA transduction was used to establish cells with stable DANCR knockdown, and silenced cells were used to initiate lung tumor xenografts, followed by monitoring tumor growth. RESULTS: DANCR upregulation was seen in lung cancer, particularly in high-grade lung cancer tissues and aggressive cancer cells. Ectopic DANCR expression induced lung cancer cell proliferation and colony formation, whereas DANCR silencing induced opposing effects. The miR-216a level in cancer cells was negatively correlated with DANCR expression. The DANCR knockdown reduced the growth of tumor xenografts in vivo. CONCLUSION: DANCR upregulation is a potential indicator of aggressive lung cancer. Silencing of DANCR has great potential as a potent therapeutic strategy in lung cancer.

LncRNA PCAT-1 promotes tumour growth and chemoresistance of oesophageal cancer to cisplatin.

Oesophageal cancer (OC) is one of the most fatal malignancies in the world, and chemoresistance restricts the therapeutic outcome of OC. Long noncoding RNA (lncRNA) was reported to play roles in multiple cancer types. Yet, the function of lncRNA in chemoresistance of OC has not been reported. A lncRNA gene, PCAT-1, showed higher expression in OC tissues, especially higher in secondary OC compared with normal mucosa tissues. Overexpression of PCAT-1 increased the proliferation rate and growth of OC cells. Inhibition of PCAT-1 decreased proliferation and growth of OC cells, and increased cisplatin chemosensitivity. In a mouse OC xenograft model, PCAT-1 inhibition repressed OC growth in vivo. Therefore, PCAT-1 may potentially serve as a therapeutic target for treating OC. PCAT-1 promotes development of OC and represses the chemoresistance of OC to cisplatin, and silencing of PCAT-1 may be a therapeutic strategy for treating OC.

MicroRNA-124 suppresses proliferation and glycolysis in non-small cell lung cancer cells by targeting AKT-GLUT1/HKII.

Non-small cell lung cancer accounts for 85% of all types of lung cancer and is the leading cause of worldwide cancer-associated mortalities. MiR-124 is epigenetically silenced in various types of cancer and plays important roles in tumor development and progression. MiR-124 was also significantly downregulated in non-small cell lung cancer patients. Glycolysis has been considered as a feature of cancer cells; hypoxia-inducible factor 1-alpha/beta and Akt are key enzymes in the regulation of glycolysis and energy metabolism in cancer cells. However, the role of miR-124 in non-small cell lung cancer cell proliferation, glycolysis, and energy metabolism remains unknown. In this research, cell proliferation was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; furthermore, glucose consumption and lactic acid production were assessed; adenosine triphosphate content and NAD+/NADH were also detected. These tests were conducted using the normal non-small cell lung cancer cell line A549, which was transfected variedly with miR-mimics, miR-124 mimics, miR-124 inhibitor, pc-DNA3.1(+)-AKT1, and pc-DNA3.1(+)-AKT2 plasmid. Here, we show that miR-124 overexpression directly decreased cell growth, glucose consumption, lactate production, and energy metabolism. MiR-124 also negatively regulates glycolysis rate-limiting enzymes, glucose transporter 1 and hexokinase II. Our results also showed that miR-124 negatively regulates AKT1 and AKT2 but no regulatory effect on hypoxia-inducible factor 1-alpha/beta. Overexpression of AKT reverses the inhibitory effect of miR-124 on cell proliferation and glycolytic metabolism in non-small cell lung cancer. AKT inhibition blocks miR-124 silencing-induced AKT1/2, glucose transporter 1, hexokinase II activation, cell proliferation, and glycolytic or energy metabolism changes. In summary, this study demonstrated that miR-124 is able to inhibit proliferation, glycolysis, and energy metabolism, potentially by targeting AKT1/2-glucose transporter 1/hexokinase II in non-small cell lung cancer cells.

microRNA-214 Governs Lung Cancer Growth and Metastasis by Targeting Carboxypeptidase-D.

Lung cancer is one of the most malignant cancers with a high metastatic potential. The purpose of this study was to study the role and the underlying mechanism of miR-214 in lung cancer progression. The expression of miR-214 in normal lung and lung cancer tissue was analyzed by quantitative real-time PCR analysis. Furthermore, H1299 cells were infected with miR-214 lentivirus, and the effect of infection on cell viability and migration was analyzed. Carboxypeptidase-D (CPD), as a potential target of miR-214, was characterized in either normal lung or lung cancer tissues. The interaction of CPD expression with the tumor suppressing effect of miR-214 was characterized. We demonstrated that low miR-214 expression is a hallmark of lung cancer, especially high-grade and metastatic cancer. In vitro studies in H1299 cells confirmed that low miR-214 expression is associated with enhanced proliferation and migratory abilities. Similarly, CPD overexpression coincides with high-grade lung cancer and the CPD overexpression could reverse the inhibitory effects of miR-214. miR-214 is a tumor suppressor in lung cancer. miR-214 inhibits lung cancer progression by targeting CPD. The miR-214-CPD axis may be a therapeutic axis for lung cancer patients.