Human Lung Cancer Tissues Research Articles

"The effects of the antibody directed nanosphere carrier for the combined carmustine-busulfan in human lung cancer tissue culture QUALITY ASSURANCE OF DRUG THROUGH CHEMOMETRIC EVOLUTION BY RAMAN SPECTROSCOPY"

"The effects of the antibody directed nanosphere carrier for the combined carmustine-busulfan in human lung cancer tissue culture QUALITY ASSURANCE OF DRUG THROUGH CHEMOMETRIC EVOLUTION BY RAMAN SPECTROSCOPY"

Syntenin overexpression in human lung cancer tissue and serum is associated with poor prognosis

BackgroundLung cancer is the major malignant tumour. The present study was conducted to determine the expression level of syntenin in lung cancer tissues and serum from lung cancer patients and to explore its clinical significance.MethodsSyntenin expression levels were determined in paraffin-embedded lung cancer tissue specimens (n = 191) using immunohistochemistry. The mRNA expressions of syntenin in fresh lung cancer tissues and the paracancerous tissues were examined by RT-qPCR (n = 25). Syntenin and VEGF expression levels were measured in serum from patients with lung cancer (n = 60) and control subjects (n = 30) using ELISA. The associations between syntenin and the clinicopathological features or prognosis in 191 patients with lung cancer were analysed. The correlation between the syntenin and VEGF levels in serum from 60 lung cancer patients was analysed.ResultsThe expression levels of syntenin were significantly higher in lung cancer tissues than in paracancerous tissues based on immunohistochemistry and RT-qPCR, and elevated syntenin expression was significantly associated with tumour size (P = 0.002), TNM stage (P = 0.020), tumour distant metastasis (P = 0.033), overall survival (OS) (P = 0.002) and progression-free survival (PFS) (P = 0.001). Multivariate analysis revealed that increased expression of syntenin was an independent risk factor for OS (P = 0.006) and PFS (P < 0.001) in lung cancer patients. The expression levels of syntenin and VEGF in serum from lung cancer patients were higher than those from control subjects (P < 0.001, P < 0.001, respectively), and their expression levels were positively correlated (r = 0.49, P < 0.001).ConclusionsSyntenin expression is upregulated in lung cancer patients, and its serum expression level is positively correlated with VEGF. Moreover, syntenin overexpression was correlated with poor prognosis in patients with lung cancer.

Large-scale lipid analysis with C=C location and sn-position isomer resolving power

Lipids play a pivotal role in biological processes and lipid analysis by mass spectrometry (MS) has significantly advanced lipidomic studies. While the structure specificity of lipid analysis proves to be critical for studying the biological functions of lipids, current mainstream methods for large-scale lipid analysis can only identify the lipid classes and fatty acyl chains, leaving the C=C location and sn-position unidentified. In this study, combining photochemistry and tandem MS we develop a simple but effective workflow to enable large-scale and near-complete lipid structure characterization with a powerful capability of identifying C=C location(s) and sn-position(s) simultaneously. Quantitation of lipid structure isomers at multiple levels of specificity is achieved and different subtypes of human breast cancer cells are successfully discriminated. Remarkably, human lung cancer tissues can only be distinguished from adjacent normal tissues using quantitative results of both lipid C=C location and sn-position isomers.

Overexpression of Krüppel-Like Factor 4 Suppresses Migration and Invasion of Non-Small Cell Lung Cancer Through c-Jun-NH2-Terminal Kinase/Epithelial-Mesenchymal Transition Signaling Pathway.

Krüppel-like factor 4 (KLF4) is a transcription factor and plays a vital role in cancer initiation and development. However, the role of Krüppel-like factor 4 in the metastasis of non-small cell lung cancer (NSCLC) is not clear. Here, we demonstrated that the expression of Krüppel-like factor 4 was significantly decreased in human non-small cell lung cancer tissues compared with that in normal tissues using Western blot. We performed immunohistochemical staining and observed the decreased expression of Krüppel-like factor 4 in human lung cancer tissues, and metastatic tumor tissues located in the trachea and main bronchus. We also found that the E-cadherin expression was decreased, while vimentin expression was increased in human NSCLC tissues and metastatic tumor tissues located in the trachea and main bronchus. Additionally, enforced expression of Krüppel-like factor 4 in mouse lungs significantly inhibited the metastasis of circulating Lewis lung carcinoma cells to the lungs by attenuating mesenchymal-epithelial transition (MET). Furthermore, cell scratch assays and Matrigel invasion assays revealed that overexpression of Krüppel-like factor 4 inhibited the migration and invasion of non-small cell lung cancer cell lines A549, H1299, H226, and H1650 cells. Moreover, overexpression of Krüppel-like factor 4 attenuated TGF-β1-induced epithelial-mesenchymal transition (EMT) in A549, and inhibited the phosphorylation of c-Jun-NH2-terminal kinase (JNK), an important pathway in metastasis in non-small cell lung cancer. Our in vivo and in vitro findings illustrate that Krüppel-like factor 4 inhibited metastasis and migration of non-small cell lung cancer, and indicate that Krüppel-like factor 4 could be a potential therapeutic target for the treatment of non-small cell lung cancer.

Transcription factor RUNX3 promotes CD8+ T cell recruitment by CCL3 and CCL20 in lung adenocarcinoma immune microenvironment.

Considering the existence of immune-desert in tumor microenvironment, the clinical efficacy of immunotherapy for lung adenocarcinoma is limited. This study aims to investigate the ability of transcription factors in regulating tumor immune microenvironment in lung adenocarcinoma. RNA-seq data were collected from the The Cancer Genome Atlas database. The relationships between transcription factors and immune infiltrates were assessed. Runt-related transcription factor 3 (RUNX3)-associated immune pathways were investigated by the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and Gene set enrichment analysis. Upregulated chemokines in the RUNX3-overexpressed cell line were determined by quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay. These chemokines were further confirmed in RUNX3-downregulated cell lines. Immunochemistry was conducted to determine the expression of RUNX3, CCL3, CCL20, and the numbers of CD8+ T lymphocytes in human lung cancer tissues. Chemokine receptors in CD8+ T cells were explored by flow cytometry and immunofluorescence. T cell recruitment was investigated by transwell assay. After screening 406 transcription factors, RUNX3 was found strongly correlated T cells, cytotoxic lymphocytes, and CD8+ T cells. RUNX3 was associated with a variety of immunomodulators, including LAG3, CTLA-4, PD-1, and TIGIT. More importantly, RUNX3 was involved in immune-related pathways, especially immune cell migration-related pathways. Further investigation exhibited RUNX3 could upregulate CCL3 and CCL20 whose receptors CCR5 and CCR6 were upregulated in CD8+ effector T cells, while downregulation of RUNX3 decreased the expression of CCL3 and CCL20 and the infiltration of CD8+ T cells in RUNX3-downregulated lung cancer cell lines. Immunochemistry exhibited positive correlations of RUNX3 with CCL3 and CD8+ T cells in clinical lung adenocarcinoma samples. The chemotaxis assay proved RUNX3 could promote CD8+ T cell recruitment by upregulating CCL3 and CCL20. This study unearths RUNX3 related molecular mechanisms of tumor immune microenvironment and may reverse the immune-desert condition in lung adenocarcinoma and be combined with immune checkpoint blockade and adoptive cell therapy.

VCAM-1 secreted from cancer-associated fibroblasts enhances the growth and invasion of lung cancer cells through AKT and MAPK signaling.

Several studies have indicated that cancer-associated fibroblasts (CAFs) could promote cancer progression in many malignancies. However, the mechanism by which CAFs promote the growth and metastasis of lung cancer remains poorly defined. In the present study, CAFs and normal fibroblasts (NFs) were isolated from human lung cancer and adjacent tissue. The data showed that the conditional medium (CM) of CAFs could increase the proliferation, migration and invasion of lung cancer cells. Vascular cell adhesion molecule-1 (VCAM-1) showed a higher expression in CAF-CM than NF-CM, and blocking VCAM-1 in CAF-CM attenuated the proliferation and invasion of cancer cells. Further, the results showed that VCAM-1 secreted from CAFs activated AKT and MAPK signaling via receptor α4β1 integrin (very-late antigen (VLA)-4) in lung cancer cells. Moreover, CAFs promoted VCAM-1 expression and tumor growth in vivo. Additionally, bioinformatics analysis indicated a positive correlation on the CAF marker protein alpha-smooth muscle actin (α-SMA) and VCAM-1 expression, which was associated with a poor prognosis in lung cancer patients. These findings demonstrate that the VCAM-1 secreted from CAFs enhances growth and invasion by activating the AKT and MAPK signaling of lung cancer cells.

Tizanidine (Hydrochloride) Inhibits A549 Lung Cancer Cell Proliferation and Motility Through Regulating Nischarin.

PurposeTizanidine hydrochloride (TZN) is a centrally acting α2-adrenergic agonist. In this study, we aimed to explore the role of TZN on human lung cancer and to elucidate its underlying mechanisms.MethodsThe effect of TZN treatment in A549 cell proliferation, migration, invasion and apoptosis was evaluated by CCK8, transwell and flow cytometer assays. The expression of apoptosis-related proteins and the activation of AKT and Wnt3a/β-catenin pathways were detected by Western blot. From the data of DrugBank, TZN could act as an agonist to target Nischarin in humans. We next investigated the function of Nischarin receptor in lung cancer and its role in the anti-tumor activity of TZN.ResultsThe treatment of TZN inhibited the proliferation, migration and invasion of A549 cells, and induced apoptosis. These results were further confirmed by that TZN treatment increased the Bax/Bcl-2 ratio in A549 cells. We also observed that TZN treatment changed the expression and phosphorylation of proteins of AKTand Wnt3a/β-catenin signaling pathway members. By bioinformatics analysis, we found that Nischarin was down-regulated in human lung cancer tissues and patients with high Nischarin expression had a better survival. Moreover, Nischarin functioned as a tumor suppressor in the survival and metastasis of A549 cells through the regulation of AKT and Wnt3a/β-catenin pathways. Knockdown of Nischarin promoted the proliferation, invasion, migration of A549 cells and inhibited the apoptosis, which were reversed by the TZN treatment.ConclusionSummary, our data revealed that treatment of TZN inhibited the growth of lung cancer cell line A549 and may be used as a novel strategy for lung cancer therapy.

Cyclin K interacts with β-catenin to induce Cyclin D1 expression and facilitates tumorigenesis and radioresistance in lung cancer.

Rationale: Radioresistance remains the major cause of local relapse and distant metastasis in lung cancer. However, the underlying molecular mechanisms remain poorly defined. This study aimed to investigate the role and regulatory mechanism of Cyclin K in lung cancer radioresistance.Methods: Expression levels of Cyclin K were measured by immunohistochemistry in human lung cancer tissues and adjacent normal lung tissues. Cell growth and proliferation, neutral comet and foci formation assays, G2/M checkpoint and a xenograft mouse model were used for functional analyses. Gene expression was examined by RNA sequencing and quantitative real-time PCR. Protein-protein interaction was assessed by immunoprecipitation and GST pull-down assays.Results: We report that Cyclin K is frequently overexpressed and correlates with poor prognosis in lung cancer patients. Functionally, we demonstrate that Cyclin K depletion results in reduced proliferation, defective G2/M checkpoint and enhanced radiosensitivity in lung cancer. Mechanistically, we reveal that Cyclin K interacts with and promotes the stabilization of β-catenin protein, thereby upregulating the expression of Cyclin D1. More importantly, we show that Cyclin D1 is the major effector that mediates the biological functions of Cyclin K in lung cancer.Conclusions: These findings suggest that Cyclin K positively modulates the β-catenin/Cyclin D1 axis to promote tumorigenesis and radioresistance in lung cancer, indicating that Cyclin K may represent a novel attractive biomarker for lung cancer radiotherapy.

Isoorientin Decreases Cell Migration via Decreasing Functional Activity and Molecular Expression of Proton-Linked Monocarboxylate Transporters in Human Lung Cancer Cells.

Aggressive tumor cells mainly rely on glycolysis, and further release vast amounts of lactate and protons by monocarboxylate transporter (MCT), which causes a higher intracellular pH (pHi) and acidic extracellular pH. Isoorientin, a principle flavonoid compound extracted from several plant species, shows various pharmacological activities. However, effects of isoorientin on anticancer and MCT await to explore in human lung cancer cells. Human lung cancer tissues were obtained from cancer patients undergoing surgery, while the human lung adenocarcinoma cells (A549) were bought commercially. Change of pHi was detected by microspectrofluorometry method with a pH-sensitive fluorescent dye, BCECF. MTT and wound-healing assay were used to detect the cell viability and migration, respectively. Western blot techniques and immunocytochemistry staining were used to detect the protein expression. Our results indicated that the expression of MCTs1/4 and CD147 were upregulated significantly in human lung tissues. In experiments of A549 cells, under HEPES-buffer, the resting pHi was 7.47, and isoorientin (1-300M) inhibited functional activity of MCT concentration-dependently (up to %). Pretreatment with isoorientin (3-100M) for 24h, MCT activity and cell migration were significantly inhibited (% and %, respectively), while the cell viability was not affected. Moreover, the expression of MCTs1/4, CD147, and matrix metalloproteinase (MMP) 2/9 were significantly down regulated. In summary, MCTs1/4 and CD147 are significantly upregulated in human lung adenocarcinoma tissues, and isoorientin inhibits cells-migration by inhibiting activity/expression of MCTs1/4 and MMPs2/9 in human lung cancer cells. These novel findings suggest that isoorientin could be a promising pharmacological agent for lung cancer.

DDIAS promotes STAT3 activation by preventing STAT3 recruitment to PTPRM in lung cancer cells

DNA damage-induced apoptosis suppressor (DDIAS) regulates cancer cell survival. Here we investigated the involvement of DDIAS in IL-6–mediated signaling to understand the mechanism underlying the role of DDIAS in lung cancer malignancy. We showed that DDIAS promotes tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3), which is constitutively activated in malignant cancers. Interestingly, siRNA protein tyrosine phosphatase (PTP) library screening revealed protein tyrosine phosphatase receptor mu (PTPRM) as a novel STAT3 PTP. PTPRM knockdown rescued the DDIAS-knockdown-mediated decrease in STAT3 Y705 phosphorylation in the presence of IL-6. However, PTPRM overexpression decreased STAT3 Y705 phosphorylation. Moreover, endogenous PTPRM interacted with endogenous STAT3 for dephosphorylation at Y705 following IL-6 treatment. As expected, PTPRM bound to wild-type STAT3 but not the STAT3 Y705F mutant. PTPRM dephosphorylated STAT3 in the absence of DDIAS, suggesting that DDIAS hampers PTPRM/STAT3 interaction. In fact, DDIAS bound to the STAT3 transactivation domain (TAD), which competes with PTPRM to recruit STAT3 for dephosphorylation. Thus we show that DDIAS prevents PTPRM/STAT3 binding and blocks STAT3 Y705 dephosphorylation, thereby sustaining STAT3 activation in lung cancer. DDIAS expression strongly correlates with STAT3 phosphorylation in human lung cancer cell lines and tissues. Thus DDIAS may be considered as a potential biomarker and therapeutic target in malignant lung cancer cells with aberrant STAT3 activation.

Expression of CHPF modulates cell proliferation and invasion in lung cancer.

Lung cancer is the most common malignancy worldwide and is characterized by rapid progression, aggressive behavior, frequent recurrence, and poor prognosis. The TCGA database indicates that chondroitin polymerizing factor (CHPF) is overexpressed in human lung cancer tissues compared with normal tissues and this overexpression corresponds to shorter overall survival in lung cancer patients. In this study, to investigate the function of CHPF in lung cancer, lentiviral vectors expressing CHPF shRNA were stably transduced into A549 and H1299 cells. Compared to shCtrl cells, CHPF knockdown cells had significantly reduced proliferation. Furthermore, the silencing of CHPF in A549 and H1299 cells resulted in apoptotic induction, which led to decreased colony formation. Wound healing and transwell invasion assays revealed that CHPF could positively regulate the migration of lung cancer cells. The tumorigenic role of CHPF was also validated in nude mouse xenograft models. Affymetrix gene chip analysis indicated that CHPF regulated the proliferation and invasion of lung cancer cells through CDH1, RRM2, MKI67, and TNFRSF10B. We thus highlight CHPF as a novel target for lung cancer treatment.

Silence of S1 RNA binding domain 1 represses cell growth and promotes apoptosis in human non-small cell lung cancer cells.

To investigate the expression of S1 RNA binding domain 1 (SRBD1) in non-small cell lung cancer tissue and the effects of SRBD1 silencing on the biological behaviors of human non-small cell lung cancer cells, and to explore the molecular mechanism of SRBD1functions in human non-small cell lung cancer cells. Expressions of SRBD1 in human non-small cell lung cancer tissues and cell lines were examined by immunostaining and RT-PCR. shRNAs of SRBD1 were chemically synthesized and transfected into A549 and NCI-H1299 cells by lentivirus. Cell proliferation was assayed by cell counting, MTT and clone formation. Cell apoptosis was assayed by flow cytometry. Tumorigenicity was assessed by cell injection into BALB/c athymic nude mouse. Gene chip analysis was employed to explore genomic changes in A549 cells. Potential classical signaling pathways, upstream regulators and gene interaction networks were analyzed by Ingenuity Pathway Analysis, and verified by western blot analysis. SRBD1 was specifically expressed in human squamous cell carcinoma and highly expressed in lung cancer cell lines, NCI-H1299, A549 and NCI-H1975. SRBD1 directed-shRNA (shSRBD1) effectively reduced the expression of SRBD1 in A549 and NCI-H1299 cells. SRBD1 silencing inhibited cell proliferation, and promoted cell apoptosis in non-small cell lung cancer cells, and suppressed tumorigenesis in a nude mouse model. In addition, we found silencing of SRBD1 expression resulted in marked changes in gene expression in A549 cells. Besides, in shSRBD1 group, the protein levels of EPS 15, IGF1R, MYC, PYCR1 and HNRNPA0 were downregulated, and the expressions of several classical factors involved in the growth and apoptosis of cancer cells were also decreased. We found that SRBD1 were specifically expressed in non-small cell lung cancer tissue. Silencing of SRBD1 inhibits cell growth and promotes cell apoptosis in non-small cell lung cancer cells, and suppresses tumorigenesis in vivo, suggesting that SRBD1 may be a new diagnostic indicator and therapeutic target of non-small cell lung cancer.

RETRACTED ARTICLE: N6-methyladenosine induced miR-143-3p promotes the brain metastasis of lung cancer via regulation of VASH1

BackgroundBrain metastasis (BM) is one of the principal causes of mortality for lung cancer patients. While the molecular events that govern BM of lung cancer remain frustrating cloudy.MethodsThe miRNA expression profiles are checked in the paired human BM and primary lung cancer tissues. The effect of miR-143-3p on BM of lung cancer cells and its related mechanisms are investigated.ResultsmiR-143-3p is upregulated in the paired BM tissues as compared with that in primary cancer tissues. It can increase the invasion capability of in vitro blood brain barrier (BBB) model and angiogenesis of lung cancer by targeting the three binding sites of 3’UTR of vasohibin-1 (VASH1) to inhibit its expression. Mechanistically, VASH1 can increase the ubiquitylation of VEGFA to trigger the proteasome mediated degradation, further, it can endow the tubulin depolymerization through detyrosination to increase the cell motility. m6A methyltransferase Mettl3 can increase the splicing of precursor miR-143-3p to facilitate its biogenesis. Moreover, miR-143-3p/VASH1 axis acts as adverse prognosis factors for in vivo progression and overall survival (OS) rate of lung cancer.ConclusionsOur work implicates a causal role of the miR-143-3p/VASH1 axis in BM of lung cancers and suggests their critical roles in lung cancer pathogenesis.

Highly multiplexed immunofluorescence images and single-cell data of immune markers in tonsil and lung cancer

In this data descriptor, we document a dataset of multiplexed immunofluorescence images and derived single-cell measurements of immune lineage and other markers in formaldehyde-fixed and paraffin-embedded (FFPE) human tonsil and lung cancer tissue. We used tissue cyclic immunofluorescence (t-CyCIF) to generate fluorescence images which we artifact corrected using the BaSiC tool, stitched and registered using the ASHLAR algorithm, and segmented using ilastik software and MATLAB. We extracted single-cell features from these images using HistoCAT software. The resulting dataset can be visualized using image browsers and analyzed using high-dimensional, single-cell methods. This dataset is a valuable resource for biological discovery of the immune system in normal and diseased states as well as for the development of multiplexed image analysis and viewing tools.

FOXD1 and Gal-3 Form a Positive Regulatory Loop to Regulate Lung Cancer Aggressiveness.

Dysregulation of forkhead box D1 (FOXD1) is known to promote tumor progression; however, its molecular mechanism of action is unclear. Based on microarray analysis, we identified galectin-3/LGALS3 (Gal-3) as a potential downstream target of FOXD1, as FOXD1 transactivated Gal-3 by interacting with the Gal-3 promoter to upregulate Gal-3 in FOXD1-overexpressing CL1-0 lung cancer cells. Ectopic expression of FOXD1 increased the expression of Gal-3 and the growth and motility of lung cancer cells, whereas depletion of Gal-3 attenuated FOXD1-mediated tumorigenesis. ERK1/2 interacted with FOXD1 in the cytosol and translocated FOXD1 into the nucleus to activate Gal-3. Gal-3 in turn upregulated FOXD1 via the transcription factor proto-oncogene 1 (ETS-1) to transactivate FOXD1. The increase in ETS-1/FOXD1 expression by Gal-3 was through Gal-3-mediated integrin-β1 (ITGβ1) signaling. The overexpression of both FOXD1 and Gal-3 form a positive regulatory loop to promote lung cancer aggressiveness. Moreover, both FOXD1 and Gal-3 were positively correlated in human lung cancer tissues. Our findings demonstrated that FOXD1 and Gal-3 form a positive feedback loop in lung cancer, and interference of this loop may serve as an effective therapeutic target for the treatment of lung cancers, particularly those related to dysregulation of Gal-3.

Vasorin/ATIA Promotes Cigarette Smoke–Induced Transformation of Human Bronchial Epithelial Cells by Suppressing Autophagy-Mediated Apoptosis

BACKGROUND: Escaping cell death pathways is an important event during carcinogenesis. We previously identified anti-TNFα-induced apoptosis (ATIA, also known as vasorin) as an antiapoptotic factor that suppresses reactive oxygen species (ROS) production. However, the role of vasorin in lung carcinogenesis has not been investigated. METHODS: Vasorin expression was examined in human lung cancer tissues with immunohistochemistry and database analysis. Genetic and pharmacological approaches were used to manipulate protein expression and autophagy activity in human bronchial epithelial cells (HBECs). ROS generation was measured with fluorescent indicator, apoptosis with release of lactate dehydrogenase, and cell transformation was assessed with colony formation in soft agar. RESULTS: Vasorin expression was increased in human lung cancer tissues and cell lines, which was inversely associated with lung cancer patient survival. Cigarette smoke extract (CSE) and benzo[a]pyrene diol epoxide (BPDE)–induced vasorin expression in HBECs. Vasorin knockdown in HBECs significantly suppressed CSE-induced transformation in association with enhanced ROS accumulation and autophagy. Scavenging ROS attenuated autophagy and cytotoxicity in vasorin knockdown cells, suggesting that vasorin potentiates transformation by impeding ROS-mediated CSE cytotoxicity and improving survival of the premalignant cells. Suppression of autophagy effectively inhibited CSE-induced apoptosis, suggesting that autophagy was pro-apoptotic in CSE-treated cells. Importantly, blocking autophagy strongly potentiated CSE-induced transformation. CONCLUSION: These results suggest that vasorin is a potential lung cancer–promoting factor that facilitates cigarette smoke–induced bronchial epithelial cell transformation by suppressing autophagy-mediated apoptosis, which could be exploited for lung cancer prevention.

PRMT5 Promotes Human Lung Cancer Cell Apoptosis via Akt/Gsk3β Signaling Induced by Resveratrol

Protein arginine methyltransferase 5 (PRMT5) is implicated in various types of human cancer and tumor development, especially in lung cancer. Nevertheless, it is still unclear whether suppression of PRMT5 could promote lung cancer cell apoptosis and chemosensitivity induced by resveratrol, and the underlying molecular mechanism remains completely unknown. Here, we showed that PRMT5 was overexpressed in human lung cancer tissues and different types of lung cancer cell lines. Moreover, we constructed PRMT5 stable knockdown cell lines (A549 and ASCT-a-1) and investigated the roles of PRMT5 and the related signaling pathway in lung cancer cell apoptosis induced by resveratrol. Our results indicated that inhibition or down-regulation of PRMT5 by GSK591, a PRMT5-specific inhibitor, or shRNAs markedly enhanced cell apoptosis and chemosensitivity stimulated by resveratrol. Further investigation showed that inhibition or down-regulation of PRMT5 further reduced Akt/GSK3β phosphorylation and the downstream targets cyclin D1 and E1 expression upon resveratrol treatment. Our findings suggest that PRMT5 is a pivotal mediator for human lung cancer cell death induced by resveratrol, which also reveals that PRMT5 may serve as a new therapeutic target for the treatment of human lung cancer.

Expression of neuritin in human lung squamous cell carcinoma

Background: This study aimed to investigate the expression of neuritin in four common cancers, and to explore the association between neuritin expression and the occurrence and development of cancer. Methods: We initially examined neuritin expression in human cervical, endometrial, oesophageal, and lung cancer tissues by immunohistochemistry (IHC). Based on these results, we further examined its expression in lung squamous cell carcinoma (LUSC) tissues by IHC and reverse transcription-polymerase chain reaction (RT-PCR). Results: Neuritin expression levels were higher in all cancer tissues compared with normal control tissues. Neuritin protein and gene expression levels were significantly higher in LUSC tissues compared with normal lung tissues (P<0.001), according to IHC and RT-PCR, respectively. Neuritin expression levels decreased significantly with increased clinical TNM stage (I-IV) and distant metastasis (P<0.05). Conclusion: Neuritin may have clinical value as a novel diagnostic and prognostic marker in patients with LUSC.

KLF8 overexpression promotes the growth of human lung cancer cells by promoting the expression of JMJD2A

BackgroundNon-small-cell lung cancer (lung cancer) has become one of the leading causes worldwide and the underlying mechanism is not fully understood. The transcriptional factor Kruppel like factor 8 (KLF8) is involved in the initiation, progression, transformation, and metastasis of diverse cancers. However, the roles of KLF8 in human non-small cell lung cancer remain unknown.MethodsCCK-8 kit and colony formation assay were performed to determine the cell growth of lung cancer cells. Flow cytometry analysis was used to evaluate apoptosis and cell cycle of lung cancer cells. Luciferase reporter assay was used to examine the activation of JMJD2A promoter by KLF8. Chromatin immunoprecipitation assay was performed to evaluate the binding of KLF8 to JMJD2A promoter. Western blot and polymerase chain reaction were applied to analyze the expression of interested genes.ResultsThe mRNA and protein levels of KLF8 in human non-small cell lung cancer tissues were overexpressed compared with the non-cancer tissues. KLF8 was knocked down with lentivirus-mediated short-hairpin RNA (shRNA) in human lung cancer cells (A549 and H1299 cells). The phenotypic results showed that KLF8 knockdown decreased the proliferation rate and colony formation of lung cancer cells. By contrast, lentivirus-mediated KLF8 overexpression promoted the growth of lung cancer cells (A549 and H1299 cells) and non-cancerous bronchial epithelial cell line BEAS-2B. Next, we showed that KLF8 regulated cell cycle at the G0 phase but not regulates cellular apoptosis of lung cancer cells. KLF8 regulated the expression of the cell cycle regulators P21 and CDK4 in a JMJD2A-dependent manner and JMJD2A knockdown significantly blocked the functions of KLF8 in regulating cell cycle and proliferation of lung cancer cells. Finally, we observed that KLF8 bound the promoter of JMJD2A and facilitated the expression of JMJD2A.ConclusionsOur evidence demonstrated that KLF8 upregulation in human lung cancer promotes the cell proliferation and colony formation of lung cancer cells. KLF8 binds to the promoter of JMJD2A and subsequently regulates the expression of P21 and CDK4, which contributes to the regulation of cell cycle by KLF8. KLF8 may serve as a target for the treatment of human lung cancer.

Expression of neuritin in human lung squamous cell carcinoma.

BackgroundThis study aimed to investigate the expression of neuritin in four common cancers, and to explore the association between neuritin expression and the occurrence and development of cancer.MethodsWe initially examined neuritin expression in human cervical, endometrial, oesophageal, and lung cancer tissues by immunohistochemistry (IHC). Based on these results, we further examined its expression in lung squamous cell carcinoma (LUSC) tissues by IHC and reverse transcription-polymerase chain reaction (RT-PCR).ResultsNeuritin expression levels were higher in all cancer tissues compared with normal control tissues. Neuritin protein and gene expression levels were significantly higher in LUSC tissues compared with normal lung tissues (P<0.001), according to IHC and RT-PCR, respectively. Neuritin expression levels decreased significantly with increased clinical TNM stage (I-IV) and distant metastasis (P<0.05).ConclusionNeuritin may have clinical value as a novel diagnostic and prognostic marker in patients with LUSC.