Invasion Of Lung Cancer Cells Research Articles

Cold atmospheric plasma enhances SLC7A11-mediated ferroptosis in non-small cell lung cancer by regulating PCAF mediated HOXB9 acetylation

Lung cancer is a leading cause of cancer death worldwide, with high incidence and poor survival rates. Cold atmospheric plasma (CAP) technology has emerged as a promising therapeutic approach for cancer treatment, inducing oxidative stress in malignant tissues without causing thermal damage. However, the role of CAP in regulating lung cancer cell ferroptosis remains unclear. Here, we observed that CAP effectively suppressed the growth and migration abilities of lung cancer cells, with significantly increased ferroptotic cell death, lipid peroxidation, and decreased mitochondrial membrane potential. Mechanistically, CAP regulates SLC7A11-mediated cell ferroptosis by modulating HOXB9. SLC7A11, a potent ferroptosis suppressor, was markedly reduced by HOXB9 knockdown, while it was enhanced by overexpressing HOXB9. The luciferase and ChIP assays confirmed that HOXB9 can directly target SLC7A11 and regulate its gene transcription. Additionally, CAP enhanced the acetylation modification level of HOXB9 by promoting its interaction with acetyltransferase p300/CBP-associated factor (PCAF). Acetylated HOXB9 affects its protein ubiquitination modification level, which in turn affects its protein stability. Notably, the upregulation of SLC7A11 and HOXB9 mitigated the suppressive effects of CAP on ferroptosis status, cell proliferation, invasion, and migration in lung cancer cells. Furthermore, animal models have also confirmed that CAP can inhibit the progression of lung cancer in vivo. Overall, this study highlights the significance of the downregulation of the HOXB9/SLC7A11 axis by CAP treatment in inhibiting lung cancer, offering novel insights into the potential mechanisms and therapeutic strategies of CAP for lung cancer.

CASQ2 alleviates lung cancer by inhibiting M2 tumor-associated macrophage polarization and JAK/STAT pathway.

Lung cancer (LC) is a major inducer of cancer-related death. We aim to reveal the effect of Calsequestrin2 (CASQ2) on macrophage polarization and Janus kinase/signal transducer and activator of transcription (JAK/STAT)pathway in LC. Hub genes were determined from protein-protein interaction networks based on GSE21933 and GSE1987 data sets using bioinformatic analysis. Expression of hub genes was verified by real-time quantitative polymerase chain reaction (RT-qPCR). Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, wound-healing, colony formation, and transwell assays were performed to assess the impact of CASQ2 on LC cells. A xenograft mouse model was evaluated using hematoxylin-eosin, immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining to investigate the effect of CASQ2 on LC. The role of CASQ2 in regulating macrophage polarization and JAK/STAT pathway was evaluated by western blot andRT-qPCR. We screened out 155 common differentially expressed genes in GSE21933 and GSE1987 data sets. Myomesin-2, tyrosine kinase, sex determining region Y-box 2, platelet and endothelial cell adhesion molecule 1, matrix metallopeptidase 9, claudin-5, caveolin-1, CASQ2, recombinant ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 (ATP2A2), and ankyrin repeat domain 1 were identified as the hub genes with high prediction value. CASQ2 was selected as a pivotal regulator of LC. In vitro experiments and xenograft models revealed that CASQ2 overexpression suppressed proliferation, colony formation, migration, invasion of LC cells, and tumor growth in vivo. Additionally, overexpression of CASQ2 promoted the expression of M1 macrophage markers (cluster of differentiation 80 [CD80], interleukin [IL]-12, inducible nitric oxide synthase [iNOS]), while decreasing the expression of M2 macrophage markers (CD163, IL-10, Arg1) in tumor-associated macrophages and xenograft tissues. Finally, we found that overexpression of CASQ2 inhibited JAK/STAT pathway. CASQ2 is a novel biomarker, which can alleviate LC via inhibiting M2 tumor-associated macrophage polarization and JAK/STAT pathway.

Exploring the uncharted seas: Metabolite profiling unleashes the anticancer properties of Oscillatoria salina

Marine cyanobacteria offer a rich source of varied natural products with both chemical and biological diversity. Oscillatoria salina (O. salina) is a filamentous non-heterocystous marine cyanobacterium from Oscillatoriaceae family. In this investigation, we have unveiled bioactive extracts from O. salina using two distinct solvent systems, revealing significant anticancer properties. Our assessment of the organic and aqueous extracts (MCE and AE) of O. salina demonstrated pronounced antiproliferative and antimetastatic effects. Notably, this study is the first to elucidate the anticancer and anti-metastatic potential of O. salina extracts in both 2D and 3D cell culture models. Both MCE and AE induced apoptosis, hindered cell proliferation, invasion, and migration in A549 non-small cell lung cancer cells, accompanied by alterations in cell morphology and cytoskeleton collapse. Moreover, MCE and AE induced spheroid disintegration in A549 cells. Transcriptomics analysis highlighted the significant involvement of Rap1 and p53 signaling pathways in mediating the observed antitumor effects. Mass spectroscopy characterization of these extracts identified 11 compounds, some known for their anticancer potential. HPLC analysis of AE revealed six peaks with UV absorption spectra resembling phycocyanin, a cyanobacterial pigment with well-known anticancer activity. Collectively, these findings underscore the anticancer potential of MCE and AE, containing bioactive metabolites with anticancer and antimetastatic properties.

Mucosa‑associated lymphoid tissue lymphoma translocation protein 1 inhibitor, MI‑2, attenuates non‑small cell lung cancer cell proliferation, migration and invasion, and promotes apoptosis by suppressing the JNK/c‑JUN pathway.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) inhibitors are effective in attenuating the progression of several types of cancer. However, their role in lung cancer requires further investigation. Therefore, the present study aimed to explore the effect of the MALT1 inhibitor, MI-2, on the behavior of non-small cell lung cancer (NSCLC) cells and to uncover their possible underlying mechanism of action. The mRNA and protein expression levels of MALT1 were detected in the human normal lung epithelial cell line BEAS-2B, and the NSCLC cell lines, NCI-H1299, NCI-H1650, HCC827, A549 and NCI-H23. Subsequently, NCI-H1650 and A549 cells were treated with MI-2. Additionally, NCI-H1650 and A549 cells were co-treated with anisomycin, a c-JUN N-terminal kinase (JNK) pathway activator, with or without MI-2. The results illustrated that the mRNA and protein expression levels of MALT1 were significantly increased in NCI-H1299, NCI-H1650, A549 and NCI-H23 cells compared with those in BEAS-2B cells. Treatment of NCI-H1650 and A549 cells with MI-2 for 72 h reduced the optical density value as determined using the Cell Counting Kit-8 assay. Consistently, the 5-ethynyl-2'-deoxyuridine assay also showed that proliferation was reduced in MI-2-treated NSCLC cells. In addition, MI-2 downregulated B-cell lymphoma 2 (BCL2), and enhanced BCL2-associated X-protein expression and apoptotic rate in NCI-H1650 and A549 cells. These findings indicated that MI-2 could inhibit NCI-H1650 and A549 cell proliferation and promote apoptosis. Furthermore, treatment of cells with MI-2 only attenuated the migration and invasion of NCI-H1650 cells. Notably, MI-2 decreased the expression levels of phosphorylated (p)-JNK and p-c-JUN in NCI-H1650 and A549 cells, thus suggesting that MI-2 could suppress the JNK/c-JUN signaling pathway. However, NSCLC cell co-treatment with anisomycin (JNK pathway activator) reversed the effect of MI-2 on the proliferation, apoptosis and activation of the JNK/c-JUN pathway in NCI-H1650 and A549 cells. In conclusion, the present study demonstrated that the MALT1 inhibitor, MI-2, could suppress NSCLC cell proliferation, migration and invasion, and induce apoptosis via inactivating the JNK/c-JUN pathway.

TNNT1 accelerates migration, invasion and EMT progression in lung cancer cells.

Clinically, most patients with lung cancer (LC) die from tumor spread and metastasis. Specific metastasis-related molecules can provide reference for clinical prediction of efficacy, evaluation of prognosis, and search for the best treatment plan. Troponin T1 (TNNT1) is highly expressed in various cancer tissues, which affects malignant behavior of tumor cells and is related to patients' survival and prognosis. However, the role and molecular mechanism of TNNT1 in LC invasion and metastasis have not yet been investigated. Gene expression profiling interactive analysis (GEPIA) online analysis was used to analyze TNNT1 expression in LC tissues. Quantitative real-time-polymerase chain reaction (qRT-PCR) or western blot were performed to measure TNNT1 or epithelial-to-mesenchymal transition (EMT)-related and Wnt/β-catenin pathway-related protein expression in LC cells. After TNNT1 knockdown, cell scratch healing and transwell assays were introduced to assess cell migration and invasion, respectively. TNNT1 expression in LC tissues and cells was increased. TNNT1 knockdown notably impaired LC cell migration, invasion and EMT. TNNT1 knockdown inhibited Wnt/β-catenin pathway of LC cells. Lithium chloride (LiCl) addition partially restored the inhibition of TNNT1 knockdown on migration, invasion, EMT and Wnt/β-catenin of LC cells. TNNT1 knockdown attenuated LC migration, invasion and EMT, possibly through Wnt/β-catenin signaling.

UBQLN4 promotes the proliferation and invasion of non-small cell lung cancer cell by regulating PI3K/AKT pathway

BackgroundUbiquilin-4 (UBQLN4), a member of the ubiquilin family, has received limited attention in cancer research to date. Here, we investigated for the first time the functional role and mechanism of UBQLN4 in non-small cell lung cancer (NSCLC).MethodsThe Cancer Genome Atlas (TCGA) database was employed to validate UBQLN4 as a differentially expressed gene. Expression differences of UBQLN4 in NSCLC cells and tissues were assessed using immunohistochemistry (IHC) experiment and western blotting (WB) experiment. Kaplan-Meier analysis was conducted to examine the association between UBQLN4 expression and NSCLC prognosis. Functional analyses of UBQLN4 were performed through cell counting kit-8 (CCK-8), colony formation, and transwell invasion assays. The impact of UBQLN4 on tumor-associated signaling pathways was assessed using the path scan intracellular signaling array. In vivo tumorigenesis experiments were conducted to further investigate the influence of UBQLN4 on tumor formation.ResultsUBQLN4 exhibited up-regulation in both NSCLC tissues and cells. Additionally, over-expression of UBQLN4 was associated with an unfavorable prognosis in NSCLC patients. Functional loss analyses demonstrated that inhibiting UBQLN4 could suppress the proliferation and invasion of NSCLC cells in both in vitro and in vivo settings. Conversely, functional gain experiments yielded opposite results. Path scan intracellular signaling array results suggested that the role of UBQLN4 is associated with the PI3K/AKT pathway, a correlation substantiated by in vitro and in vivo tumorigenesis experiments.ConclusionWe validated that UBQLN4 promotes proliferation and invasion of NSCLC cells by activating the PI3K/AKT pathway, thereby facilitating the progression of NSCLC. These findings underscore the potential of targeting UBQLN4 as a therapeutic strategy for NSCLC.

Exosomal miR-196b secreted from bronchial epithelial cells chronically exposed to low-dose PM2.5 promotes invasiveness of adjacent and lung cancer cells

Fine particulate matter (PM2.5) is a risk factor for pulmonary diseases and lung cancer, and inhaled PM2.5 is mainly deposited in the bronchial epithelium. In this study, we investigated the effect of long-term exposure to low-dose PM2.5 on BEAS-2B cells derived from the normal bronchial epithelium. BEAS-2B cells chronically exposed to a concentration of 5 µg/ml PM2.5 for 30 passages displayed the phenotype promoting epithelial-mesenchymal transition (EMT) and cell invasion. Cellular internalization of exosomes (designated PM2.5 Exo) extracted from BEAS-2B cells chronically exposed to low-dose PM2.5 promoted cell invasion in vitro and metastatic potential in vivo. Hence, to identify the key players driving phenotypic alterations, we analyzed microRNA (miRNA) expression profiles in PM2.5 Exo. Five miRNAs with altered expression were selected: miRNA-196b-5p, miR-135a-2–5p, miR-3117–3p, miR-218–5p, and miR-497–5p. miR-196b-5p was the most upregulated in both BEAS-2B cells and isolated exosomes after PM2.5 exposure. In a functional validation study, genetically modified exosomes overexpressing a miR-196b-5p mimic induced an enhanced invasive phenotype in BEAS-2B cells. Conversely, miR-196b-5p inhibition diminished the PM2.5-enhanced EMT and cell invasion. These findings indicate that exosomal miR-196b-5p may be a candidate biomarker for predicting the malignant behavior of the bronchial epithelium and a therapeutic target for inhibiting PM2.5-triggered pathogenesis.

The Role of TGFBR3 in the Development of Lung Cancer.

The Transforming Growth Factor-β (TGF-β) mediates embryonic development, maintains cellular homeostasis, regulates immune function, and is involved in a wide range of other biological processes. TGF-β superfamily signaling pathways play an important role in cancer development and can promote or inhibit tumorigenesis. Type III TGF-β receptor (TGFBR3) is a co-receptor in the TGF-β signaling pathway, which often occurs with reduced or complete loss of expression in many cancer patients and can act as a tumor suppressor gene. The reduction or deletion of TGFBR3 is more pronounced compared to other elements in the TGF-β signaling pathway. In recent years, lung cancer is one of the major malignant tumors that endanger human health, and its prognosis is poor. Recent studies have reported that TGFBR3 expression decreases to varying degrees in different types of lung cancer, both at the tissue level and at the cellular level. The invasion, metastasis, angiogenesis, and apoptosis of lung cancer cells are closely related to the expression of TGFBR3, which strengthens the inhibitory function of TGFBR3 in the evolution of lung cancer. This article reviews the mechanism of TGFBR3 in lung cancer and the influencing factors associated with TGFBR3. Clarifying the physiological function of TGFBR3 and its molecular mechanism in lung cancer is conducive to the diagnosis and treatment of lung cancer.

Mutant TP53 promotes invasion of lung cancer cells by regulating desmoglein 3

PurposeTargeted therapies have markedly improved the prognosis of lung cancer patients; nevertheless, challenges persist, including limited beneficiary populations and the emergence of drug resistance. This study investigates the molecular mechanisms of mutant TP53 in lung cancer, aiming to contribute to novel strategies for targeted therapy.MethodsThe TCGA database was employed to delineate the mutational landscape of TP53 in lung cancer patients. Differential gene expression between TP53-mutant and wild-type patients was analyzed, followed by functional enrichment. DSG3 protein expression in lung cancer patients was assessed using IHC, and its impact on prognosis was analyzed in the TCGA database. The influence of TP53 on the downstream gene DSG3 was investigated using qPCR, ChIP-qPCR, and luciferase reporter gene assays. Protein enrichment in the DSG3 promoter region was examined through IP-MS, and the regulatory role of the HIF1-α/TP53 complex on DSG3 was explored using Co-IP, luciferase assays, and ChIP-qPCR. Molecular interactions between TP53 (R273H) and HIF1-α were detected through immunoprecipitation and molecular docking. The effects and mechanisms of DSG3 on lung cancer phenotypes were assessed through WB, transwell, and wound healing assays.ResultsTP53 mutations were present in 47.44% of patients, predominantly as missense mutations. DSG3 exhibited high expression in TP53-mutant lung cancer patients, and this elevated expression correlated with a poorer prognosis. TP53 interference led to a reduction in DSG3 mRNA expression, with TP53 mutant P53 enriching at the P2 site of the DSG3 promoter region, a recruitment facilitated by HIF1-α. The DBD region of TP53 (R273H) demonstrated interaction with HIF1-α. DSG3, activated through Ezrin phosphorylation, played a role in promoting invasion and metastasis.ConclusionsMutant TP53 facilitates lung cancer cell invasion by modulating desmoglein 3.Graphical abstractThe regulation of TP53 on DSG3 in lung cancer cell

Retracted] 2,3,5,4‑tetrahydroxy diphenylethylene‑2‑O‑glucoside inhibits the adhesion and invasion of A549 human lung cancer cells.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the data featured in Figs. 1, 4 and 5 (including western blotting data) were strikingly similar to data that had appeared in a different form in a different article by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been accepted for publication in another article prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 8900‑8906, 2017; DOI: 10.3892/mmr.2017.7680].

POLR1D silencing suppresses lung cancer cells proliferation and migration via inhibition of PI3K-Akt pathway

AimThe most common type of cancer that leads to death worldwide is lung cancer. Despite significant surgery and chemotherapy improvements, lung cancer patient’s survival rate is still poor. The RNA polymerase I subunit D (POLR1D) gene can induce various cancers. A current study reported that POLR1D plays a vital role in cancer prognosis. However, its biological function in the development of lung cancer remains unclear.MethodsReverse transcription PCR (RT-PCR) measured the relative POLR1D protein expression level in lung cancer cell lines. Lung cancer cell proliferation, migration, and invasion were analyzed by performing cell counting kit-8 (CCK-8), and transwell. The phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/AKT) signaling pathway-related protein expressions were examined by Western blotting assay.ResultsPOLR1D protein expression was elevated in lung cancer. Lung cancer cell loss-of-function tests showed that POLR1D silencing could attenuate cell viability both in SK-MES-1 and in H2170 cells. Furthermore, silencing POLR1D inhibited SK-MES-1 and H2170 cells proliferation, migration, and invasion. Moreover, SK-MES-1 and H2170 cells’ migration and invasion capacity were potentially suppressed by the knockdown of POLR1D. The progression of multiple cancers has been implicated in the PI3K/AKT pathway. Here, we observed that POLR1D silencing suppressed lung cancer progression by inhibition of the PI3K-Akt pathway.ConclusionsThe study speculated that POLR1D might provide a new potential therapeutic possibility for treating lung cancer patients via targeting PI3K/AKT.

Extracellular vesicles derived from stored red blood cell suspensions enhance invasion and migration of lung cancer cells by miR1246 and miR150-3p.

Aged red blood cell (RBC) transfusions in lung cancer patients are often related to cancer recurrence and shorter lifespans. Extracellular vesicles (EVs) accumulated in stored RBC suspensions may be one of the important influential factors. This study aims to investigate how EVs derived from RBC suspensions affect the progress of lung cancer through the most enriched microRNAs (miRNAs) previously reported in our research. EVs derived from stored RBC suspensions in Weeks 1, 3 and 5 were harvested via ultracentrifugation. Lung adenocarcinoma H1975 cells were co-cultured with EVs and transfected with miR1246 and miR150-3p mimics to evaluate alterations in their proliferation, invasion and migration abilities in vitro. Proteomics and bioinformatics were performed to predict the signalling pathway related to invasion and migration of H1975, which were verified by western blotting (WB) and flow cytometry. EVs derived from stored RBC suspensions in Weeks 3 and 5 could significantly enhance the invasion and migration ability of H1975 cells and also increase the expression of miR1246 and miR150-3p. After transfection with miR1246 and miR150-3p mimics, invasion, migration and proliferation of H1975 cells were obviously enhanced. Proteomics analysis demonstrated that EVs co-cultivation and miRNA transfection groups were both enriched in cell adhesion molecules. WB and cytometry indicated that integrin beta-1 (ITGB1) and Rap1b were increased. EVs derived from stored RBC suspensions can enhance invasion and migration ability of lung cancer cells via the most accumulated miR1246 and miR150-3p, which may increase the expression of ITGB1 through Rap1 signalling pathway.

CBX8 Promotes Epithelial-mesenchymal Transition, Migration, and Invasion of Lung Cancer through Wnt/β-catenin Signaling Pathway.

Lung cancer (LC) is primarily responsible for cancer-related deaths worldwide. Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells acquire mesenchymal features and is associated with the development of tumors. CBX8, a member of the PcG protein family, plays a critical role in various cancers, containing LC. However, specific regulatory mechanisms of CBX8 in LC progression are not fully understood. This study aimed to investigate the regulatory role of CBX8 in LC progression. Bioinformatics was used to analyze the relationship between CBX8 level and tumor and the enrichment pathway of CBX8 enrichment. qRT-PCR was used to detect the differential expression of CBX8 in LC cells and normal lung epithelial cells. The effects of knockdown or overexpression of CBX8 on the proliferation, migration and invasion of LC cells were evaluated by CCK- -8 assay and Transwell assay, and the levels of proteins associated with the EMT pathway and Wnt/ β-catenin signaling pathway were detected by western blot. Bioinformatics analysis revealed that CBX8 was highly expressed in LC and enriched on the Wnt/β-catenin signaling pathway. The expression level of CBX8 was significantly elevated in LC cells. Knockdown of CBX8 significantly inhibited cell proliferation, migration and invasion, and decreased the expression levels of EMT-related proteins and Wnt/β-catenin pathway-related proteins. Conversely, overexpression of CBX8 promoted cell proliferation, migration and invasion, and increased the expression levels of EMT-related proteins and Wnt/β-catenin pathway-related proteins. The Wnt inhibitor IWP-4 alleviated the effects produced by overexpression of CBX8. Collectively, these data demonstrated that CBX8 induced EMT through Wnt/β-- catenin signaling, driving migration and invasion of LC cells.

Accurate identification of lung cancer in the early phase by serum exosomal miR-1271-5p.

e20029 Background: Exosomal miRNAs are associated with the proliferation, migration, and invasion of lung cancer cells. We aim to investigate the clinical significance of serum exosomal miR-1271-5p in early-stage lung cancer (ESLC) mainly characterized by pulmonary nodules to push forward the prevention and treatment of lung cancer. Methods: The serum exosome (sEVs) miR-1271-5p was obtained from a total of 134 subjects from the patients with ESLC and the benign nodule (BLN) and healthy controls, and the expression level of miR-1271-5p were detected by RT-qPCR. Through analysis the clinical feature and CT (Computed Tomography) imaging finding of the subjects confirmed by pathology, independent risk factors for ESLC were obtained according to univariate and multivariate logistic regression analysis. R software was incorporated to build a mathematical prediction model of nomogram, and the clinical significance of sEVs-miR-1271-5p in the prediction and diagnosis of ESLC was verified by ROC curve. Results: The relative expression of sEVs-miR-1271-5p was lower in the patients with ESLC than the patients with BLN and healthy controls. The AUC value of the ESLC predicted by sEVs-miR-1271-5p was 0.9845 (95%CI: 0.9649-1.000, P < 0.0001). The results of multi-factor logistic regression analysis showed that gender (OR = 0.213, p = 0.046), nodule diameter (OR = 0.794, p = 0.031), lobulation (OR = 0.013, p < 0.0001), and sEVs-miR-1271-5p (OR = 0.014, p = 0.037) were independent risk factors for ESLC. Based on these independent risk factors, a prediction model for ESLC was established, with an AUC value of 0.8810 (95% CI: 0.8076-0.9553, P < 0.0001), the sensitivity, specificity, positive and negative predictive value and accuracy of the model were 85%, 80.43%, 79.07%, 86.05% and 82.56% respectively. Conclusions: Serum exosomal miR-1271-5p may break through the early diagnosis of lung cancer and provide important therapeutic targets.

Pharmacological Properties of White Mulberry (Morus alba L.) Leaves: Suppressing Migratory and Invasive Activities Against A549 Lung Cancer Cells.

Morus alba known as a white mulberry is a medicinal plant that has been used in food ingredients and traditional medicine. M. alba leaves contain various bioactive phenolic compounds, in particular chlorogenic acid (CGA), which is a major bioactive ingredient. Their anticancer potency of M. alba leaf extracts derived from Soxhlet extraction was evaluated based on cytotoxicity and antimigratory and antiinvasive properties. The dichloromethane extract exhibited the highest nitric oxide radical scavenging activity with a half-maximal inhibitory concentration (IC50) value of 780μg/mL, promising cytotoxicity against HuCCA-1, MCF-7, and A-549 cells with IC50 values of 59.18, 62.20, and 103.25μg/mL, respectively. CGA selectively inhibited the growth of MCF-7 cells with an IC50 value of 26.75μg/mL and showed potent radical scavenging activity against DPPH radicals (IC50 = 18.85μg/mL). An ethanolic extract derived from the gradient Soxhlet extraction suppressed A549 lung cancer cell migration and invasion more effectively than CGA with no migratory inhibition effect on noncancerous HaCaT cells. Furthermore, the ethanolic extract and CGA accelerated HaCaT wound closure at 20µg/mL, which was the same as allantoin. Bioactive ingredients including triterpenes, steroids, phenolics, and flavonoids were mainly detected in all extracts. The highest content of CGA (52.23g/100g dry weight) was found in the ethanolic extract derived from the gradient Soxhlet extraction. These findings show the potency of the dichloromethane extract as a cytotoxic agent against various cancer types and the ethanolic extract as an antimetastatic agent by their antimigratory and antiinvasive activities.

Citrulline facilitates the glycolysis, proliferation, and metastasis of lung cancer cells by regulating RAB3C.

Lung cancer (LC) is one of the major malignant diseases threatening human health. The study aimed to identify the effect of citrulline on the malignant phenotype of LC cells and to further disclose the potential molecular mechanism of citrulline in regulating the development of LC, providing a novel molecular biological basis for the clinical treatment of LC. The effects of citrulline on the viability, proliferation, migration, and invasion of LC cells (A549, H1299) were validated by CCK-8, colony formation, EdU, and transwell assays. The cell glycolysis was assessed via determining the glucose uptake, lactate production, ATP levels, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR). RNA-seq and molecular docking were performed to screen for citrulline-binding target proteins. Western blotting experiments were conducted to examine the expression of related signaling pathway molecules. In addition, the impacts of citrulline on LC growth in vivo were investigated by constructing mouse models. Citrulline augmented the viability of LC cells in a concentration and time-dependent manner. The proliferation, migration, invasion, glycolysis, and EMT processes of LC cells were substantially enhanced after citrulline treatment. Bioinformatics analysis indicated that citrulline could bind to RAB3C protein. Western blotting results indicated that citrulline activated the IL-6/STAT3 pathway by binding to RAB3C. In addition, animal experiments disclosed that citrulline promoted tumor growth in mice. Citrulline accelerated the glycolysis and activated the IL6/STAT3 pathway through the RAB3C protein, consequently facilitating the development of LC.

Retraction: Knockdown of TRIM65 inhibits lung cancer cell proliferation, migration and invasion: A therapeutic target in human lung cancer.

Retraction: Knockdown of TRIM65 inhibits lung cancer cell proliferation, migration and invasion: A therapeutic target in human lung cancer.

Dysregulation of lncRNA MALAT1 Contributes to Lung Cancer in African Americans by Modulating the Tumor Immune Microenvironment.

African American (AA) populations present with notably higher incidence and mortality rates from lung cancer in comparison to other racial groups. Here, we elucidated the contribution of long non-coding RNAs (lncRNAs) in the racial disparities and their potential clinical applications in both diagnosis and therapeutic strategies. AA patients had elevated plasma levels of MALAT1 and PVT1 compared with cancer-free smokers. Incorporating these lncRNAs as plasma biomarkers, along with smoking history, achieved 81% accuracy in diagnosis of lung cancer in AA patients. We observed a rise in MALAT1 expression, correlating with increased levels of monocyte chemoattractant protein-1 (MCP-1) and CD68, CD163, CD206, indicative of tumor-associated macrophages in lung tumors of AA patients. Forced MALAT1 expression led to enhanced growth and invasiveness of lung cancer cells, both in vitro and in vivo, accompanied by elevated levels of MCP-1, CD68, CD163, CD206, and KI67. Mechanistically, MALAT1 acted as a competing endogenous RNA to directly interact with miR-206, subsequently affecting MCP-1 expression and macrophage activity, and enhanced the tumorigenesis. Targeting MALAT1 significantly reduced tumor sizes in animal models. Therefore, dysregulated MALAT1 contributes to lung cancer disparities in AAs by modulating the tumor immune microenvironment through its interaction with miR-206, thereby presenting novel diagnostic and therapeutic targets.

Mechanism Research of PZD Inhibiting Lung Cancer Cell Proliferation, Invasion, and Migration based on Network Pharmacology.

A classic Chinese medicine decoction, Pinellia ternata (Thunb.) Breit.-Zingiber officinale Roscoe (Ban-Xia and Sheng-Jiang in Chinese) decoction (PZD), has shown significant therapeutic effects on lung cancer. This study aimed to explore and elucidate the mechanism of action of PZD on lung cancer using network pharmacology methods. Active compounds were selected according to the ADME parameters recorded in the TCMSP database. Potential pathways related to genes were identified through GO and KEGG analysis. The compoundtarget network was constructed by using Cytoscape 3.7.1 software, and the core common targets were obtained by protein-protein interaction (PPI) network analysis. Batch molecular docking of small molecule compounds and target proteins was carried out by using the AutoDock Vina program. Different concentrations of PZD water extracts (10, 20, 40, 80, and 160 μg/mL) were used on lung cancer cells. Moreover, MTT and Transwell experiments were conducted to validate the prominent therapeutic effects of PZD on lung cancer cell H1299. A total of 381 components in PZD were screened, of which 16 were selected as bioactive compounds. The compound-target network consisting of 16 compounds and 79 common core targets was constructed. MTT experiment showed that the PZD extract could inhibit the cell proliferation of NCI-H1299 cells, and the IC50 was calculated as 97.34 ± 6.14 μg/mL. Transwell and wound-healing experiments showed that the PZD could significantly decrease cell migration and invasion at concentrations of 80 and 160 μg/mL, respectively. The in vitro experiments confirmed that PZD had significant therapeutic effects on lung cancer cells, mainly through the PI3K/AKT signaling pathway. PZD could inhibit the cell proliferation, migration, and invasion of NCI-H1299 cells partially through the PI3K/AKT signaling pathway. These findings suggested that PZD might be a potential treatment strategy for lung cancer patients.

Retraction: Long noncoding RNA NSCLCAT1 increases non-small cell lung cancer cell invasion and migration through the Hippo signaling pathway by interacting withCDH1.

Zhao W, Zhang L, Wang X, Zhang J, Yu, H. Long noncoding RNA NSCLCAT1 increases non-small cell lung cancer cell invasion and migration through the Hippo signaling pathway by interacting with CDH1. The FASEB Journal 2019; 33: 1151-1166. https://doi.org/10.1096/fj.201800408R The above article, published online on 27 August 2018 in The FASEB Journal/Wiley Online Library (faseb.onlinelibrary.wiley.com), has been retracted with the agreement of Journal Editor-in-Chief Loren Wold and Wiley Periodicals LLC. The authors discovered errors in the published figures and were unable to replicate the reported results. They have therefore concluded the original results are unreliable.