DNA methylation of miR-138 regulates cell proliferation and EMT in cervical cancer by targeting EZH2.

BACKGROUND: Emerging evidence has identified miR-138 as a tumor suppressor that can suppress the proliferation of various cancers. Meanwhile, the cause of abnormal miR-138 expression in cervical cancer remains uncertain. This study clarified the mechanism by which miR-138 regulates proliferation, invasion, metastasis, and EMT in cervical cancer cells. RESULTS: miR-138 expression in human cervical cancer and adjacent normal tissue was measured using qPCR. SiHa and C33A cells were used to determine the function of miR-138 via miR-138 mimic or inhibitor transfection, followed by wound healing, Cell Counting Kit-8, flow cytometry, and Transwell assays. Epithelial and mesenchymal marker expression was analyzed using Western blotting. DNA methylation in the miR-138 promoter was examined using bisulfite sequencing PCR. The downstream target genes of miR-138 were identified via bioinformatics analysis and luciferase reporter assays. A tumor xenograft model was employed to validate DNA methylation-induced miR-138 downregulation and tumor growth inhibition in cervical cancer in vivo. miR-138 levels were significantly lower in cervical cancer tissues than in adjacent control tissues. Furthermore, lower miR-138 expression and higher CpG methylation in the miR-138 promoter were identified in lymph node-positive metastatic cervical cancer tumors versus that in non-metastatic tumor tissues. Upon miR-138 overexpression, cell proliferation, metastasis, invasion, and EMT were suppressed. miR-138 agomir transfection and demethylating drug treatment significantly inhibited cervical tumor growth and EMT in tumor xenograft models. DNA methylation inhibited miR-138 transcription, and enhancer of zeste homolog 2 (EZH2) downregulation mediated the tumor suppressor function of miR-138 in cervical cancer. CONCLUSION: We demonstrated that miR-138 suppresses tumor progression by targeting EZH2 in cervical cancer and uncovered the role of DNA methylation in the miR-138 promoter in its downregulation. These findings demonstrated the potential of miR-138 to predict disease metastasis and/or function as a therapeutic target in cervical cancer.

Integrated mRNA and miRNA Transcriptome Analysis Suggests a Regulatory Network for UV-B-Controlled Terpenoid Synthesis in Fragrant Woodfern (Dryopteris fragrans).

Fragrant woodfern (Dryopteris fragrans) is a medicinal plant rich in terpenoids. Ultraviolet-B (UV-B) light could increase concentration of terpenoids. The aim of this study was to analyze how UV-B regulates the terpenoid synthesis of the molecular regulatory mechanism in fragrant woodfern. In this study, compared with the control group, the content of the terpenes was significantly higher in fragrant woodfern leaves under UV-B treatment for 4 days (d). In order to identify how UV-B regulates the terpenoid metabolic mechanism in fragrant woodfern, we examined the mRNAs and small RNAs in fragrant woodfern leaves under UV-B treatment. mRNA and miRNA-seq identified 4533 DEGs and 17 DEMs in the control group compared with fragrant woodfern leaves under UV-B treatment for 4 d. mRNA-miRNA analysis identified miRNA target gene pairs consisting of 8 DEMs and 115 miRNAs. The target genes were subjected to GO and KEGG analyses. The results showed that the target genes were mainly enriched in diterpene biosynthesis, terpenoid backbone biosynthesis, plant hormone signal transduction, MEP pathway and MVA pathway, in which miR156 and miR160 regulate these pathways by targeting DfSPL and DfARF, respectively. The mRNA and miRNA datasets identified a subset of candidate genes. It provides the theoretical basis that UV-B regulates the terpenoid synthesis of the molecular regulatory mechanism in fragrant woodfern.

Transcription Factor AtOFP1 Involved in ABA-Mediated Seed Germination and Root Growth through Modulation of ROS Homeostasis in Arabidopsis.

Ovate family proteins (OFPs) are valued as a family of transcription factors that are unique to plants, and they play a pluripotent regulatory role in plant growth and development, including secondary-cell-wall synthesis, DNA repair, gibberellin synthesis, and other biological processes, via their interaction with TALE family proteins. In this study, CHIP-SEQ was used to detect the potential target genes of AtOFP1 and its signal-regulation pathways. On the other hand, Y2H and BIFC were employed to prove that AtOFP1 can participate in ABA signal transduction by interacting with one of the TALE family protein called AtKNAT3. ABA response genes are not only significantly upregulated in the 35S::HAOFP1 OE line, but they also show hypersensitivity to ABA in terms of seed germination and early seedling root elongation. In addition, the AtOFP1-regulated target genes are mainly mitochondrial membranes that are involved in the oxidative-phosphorylation pathway. Further qRT-PCR results showed that the inefficient splicing of the respiratory complex I subunit genes NAD4 and NAD7 may lead to ROS accumulation in 35S::HA-AtOFP1 OE lines. In conclusion, we speculated that the overexpression of AtOFP1 may cause the ABA hypersensitivity response by increasing the intracellular ROS content generated from damage to the intima systems of mitochondria.

Investigation of differentially expressed gene profile for cisplatin-treated lung cancer patients.

The purpose of the study was to establish a comprehensive differential gene profile for lung cancer patients treated with cisplatin compared with control patients without any chemotherapy drug treatment. The RNA sequencing data and miRNA sequencing data of 108 lung cancer patients treated with cisplatin only and 232 lung cancer patients treated without any chemotherapeutic drugs, were analyzed using differential expression, protein-protein interaction, and immune cell infiltration ratio analysis. Compared with control patients, the cisplatin-treated patients demonstrated 336 differentially expressed genes, which included 48 upregulated genes and 288 downregulated genes. Meanwhile, 12 differentially expressed miRNAs (DEMs), including 7 upregulated miRNAs and 5 downregulated miRNAs showed a differentially expressed pattern. With further instigation, five miRNAs (hsa-miR-548ah, hsa-miR-466, hsa-miR-552, hsa-miR-371a, and hsa-miR-4445) were suggested to be the key targets in the cisplatin-treated patients. At the same time, we also found a significant correlation between the cisplatin treatment and six immune checkpoints including programmed cell death ligand. This study helped us better understand the potential targets and underline molecular mechanisms for cisplatin treatment and provided references to eliminate existing side effects in the future.

Seasonal concentration variation and potential influencing factors of organophosphorus flame retardants in a wastewater treatment plant.

Organophosphate flame retardants (OPFRs) in both of water and sludge phase of influent and effluent of the STP were investigated in Beijing of China in five seasons. Total OPFRs concentrations in water phase of influent in five seasons were between 600 and 838 ng/L, where total OPFRs concentration was the lowest in summer of 2018. In water phase of influent and effluent, two chlorinated OPFRs (TCEP and TCPP) were major. Alkyl OPFRs decreased the most in water phase from influent to effluent. In sludge phase, the OPFRs amounts in winter were the lowest. The main OPFRs in sludge phase were TEHP and EHDP, which can be explained by the two OPFRs properties (log Kow and log Koc). Higher the values of the log Kow and log Koc of OPFRs, more amounts in sludge phase. The mass flow of OPFRs in influent were analysed by Principal Component Analysis (PCA), indicating that the influent amounts of TCEP, TDCP, TCPP and DCP were main OPFRs in four seasons to influence the characteristics of influent. Compared to OPFRs reduction in some STPs in other countries, alkyl and aryl OPFRs reduction rates were higher than chlorinated OPFRs. TBEP, TEHP and TPHP can always be effectively removed in different seasons and different STPs. The analysis methods of Pearson correlation and linear correlation were processed to check the possible factors affecting OPFRs reduction in STP. OPFRs reduction was related to some STP working parameters. Significant correlation also was found between OPFRs properties and reduction.

Transcriptomic Analysis and Specific Expression of Transcription Factor Genes in the Root and Sporophyll of Dryopteris fragrans (L.) Schott.

Background: Dryopteris fragrans, which is densely covered with glandular trichomes, is considered to be one of the ferns with the most medicinal potential. The transcriptomes from selected tissues of D. fragrans were collected and analyzed for functional and comparative genomic studies. The aim of this study was to determine the transcriptomic characteristics of wild D. fragrans sporangium in tissues from the SR (root), SL (sporophyll), and TRL (sporophyll with glandular trichomes removed). Results: Cluster analysis identified genes that were highly expressed in an organ-specific manner according to read mapping, feature counting, and normalization. The functional map identified gene clusters that can uniquely describe the function of each tissue. We identified a group of three tissue-specific transcription factors targeting the SL, SR, and TRL. In addition, highly expressed transcription factors (TFs) were found in each tissue-specific gene cluster, where ERF and bHLH transcription factors were the two types showing the most distinct expression patterns between the three different tissues. The specific expression of transcription factor genes varied between the different types of tissues. The numbers of transcription factors specifically expressed in the roots and sporophylls were 60 and 30, respectively, while only seven were found for the sporophylls with glandular trichomes removed. The expression of genes known to be associated with the development of glandular trichomes in flowering plants, including MIXTA, ATML1, and MYB106, were also validated and are discussed. In particular, a unigene encoding MIXTA was identified and exhibited the highest expression level in SL in D. fragrans. Conclusions: This study is the first report of global transcriptomic analysis in different tissues of D. fragrans, and the first to discuss these findings in the context of the development of homologous glandular trichomes. These results set the stage for further research on the development, stress resistance, and secondary metabolism of D. fragrans glandular trichomes.

Covalent Linkage of an R-ω-Transaminase to a d-Amino Acid Oxidase through Protein Splicing to Enhance Enzymatic Catalysis of Transamination.

R-ω-Transaminases (RTAs) catalyse the conversion of R-configured amines [e.g., (R)-1-phenylethylamine] into the corresponding ketones (e.g., acetophenone), by transferring an amino group from an amino donor [e.g., (R)-1-phenylethylamine] onto an amino acceptor (e.g., pyruvate), resulting in a co-product (e.g., d-alanine). d-Alanine can be deaminated back to pyruvate by d-amino acid oxidase (DAAOs). Here, through in vivo subunit splicing, the N terminus of an RTA subunit (RTAS ) was specifically ligated to the C terminus of a DAAO subunit (DAAOS ) through native peptide bonds (RTA&DAAO). RTAS is in close proximity to DAAOS , at a molecular-scale distance. Thus the transfer of pyruvate and d-alanine between RTA and DAAO can be directional and efficient. Pyruvate→d-alanine→pyruvate cycles are efficiently formed, thus promoting the forward transamination reaction. In a different, in vitro noncovalent approach, based on coiled-coil association, the RTAS N terminus was specifically associated with the DAAOS C terminus (RTA#DAAO). In addition, the two mixed individual enzymes (RTA+DAAO) were also studied. RTA&DAAO has a shorter distance between the paired subunits (RTAS -DAAOS ) than RTA#DAAO, and the number of the paired subunits is higher than in the case of RTA#DAAO, whereas RTA+DAAO cannot form the paired subunits. RTA&DAAO exhibited a transamination catalysis efficiency higher than that of RTA#DAAO and much higher than that of RTA+DAAO.

Combined Application of Leguminous Green Manure and Straw Determined Grain Yield and Nutrient Use Efficiency in Wheat-Maize-Sunflower Rotations System in Northwest China.

Leguminous green manure (LGM) has a reputation for improving crop productivity. However, little is known about the beneficial interactions with straw on crop yield and nutrient (N, P, K) use efficiency. Herein, a 9-year field experiment (from 2015 to 2023) containing three treatments-(1) chemical fertilizer as the control (CK), (2) NPK + straw return (Straw) and (3) NPK + straw return with LGM (Straw + LGM)-was conducted to investigate whether the combined application of LGM and straw can increase productivity and nutrient use efficiency in the wheat-maize-sunflower diversified cropping rotation. The results showed that in the third rotation (2021-2023), Straw + LGM significantly increased wheat yield by 10.2% and maize yield by 19.9% compared to CK. The total equivalent yield under Straw + LGM was the highest (26.09 Mg ha-1), exceeding Straw and CK treatments by 2.7% and 12.3%, respectively. For each 2 Mg ha-1 increase in straw returned to the field, sunflower yield increased by 0.2 Mg ha-1, whereas for each 1 Mg ha-1 increase in LGM yield from the previous crop, sunflower yield increased by 0.45 Mg ha-1. Compared to CK, the co-application of LGM and straw increased the N use efficiency of maize in the first and third rotation cycle by 70.6% and 55.8%, respectively, and the P use efficiency by 147.8% in the third rotation cycle. Moreover, Straw treatment led to an increase of net income from wheat and sunflower by 14.5% and 44.6%, while Straw + LGM increased the net income from maize by 15.8% in the third rotation cycle. Combining leguminous green manure with a diversified cropping rotation has greater potential to improve nutrient use efficiency, crop productivity and net income, which can be recommended as a sustainable agronomic practice in the Hetao District, Northwest China.

Coupling of Perinuclear Actin Cap and Nuclear Mechanics in Regulating Flow-Induced Yap Spatiotemporal Nucleocytoplasmic Transport.

Mechanical forces, including flow shear stress, govern fundamental cellular processes by modulating nucleocytoplasmic transport of transcription factors like Yes-associated Protein (YAP). However, the underlying mechanical mechanism remains elusive. In this study, it is reported that unidirectional flow induces biphasic YAP transport with initial nuclear import, followed by nuclear export as actin cap formation and nuclear stiffening. Conversely, pathological oscillatory flow induces slight actin cap formation, nuclear softening, and sustained YAP nuclear localization. To elucidate the disparately YAP spatiotemporal distribution, a 3D mechanochemical model is developed, which integrates flow sensing, cytoskeleton organization, nucleus mechanotransduction, and YAP transport. The results unveiled that despite the significant localized nuclear stress imposed by the actin cap, its inherent stiffness counteracts the dispersed contractile stress exerted by conventional fibers on the nuclear membrane. Moreover, alterations in nuclear stiffness synergistically regulate nuclear deformation, thereby governing YAP transport. Furthermore, by expanding the single-cell model to a collective vertex framework, it is revealed that the irregularities in actin cap formation within individual cells have the potential to induce topological defects and spatially heterogeneous YAP distribution in the cellular monolayer. This work unveils a unified mechanism of flow-induced nucleocytoplasmic transport, providing a linkage between transcription factor localization and mechanical stimulation.

Interpretable deep learning survival predictive tool for small cell lung cancer.

Background: Small cell lung cancer (SCLC) is an aggressive and almost universally lethal neoplasm. There is no accurate predictive method for its prognosis. Artificial intelligence deep learning may bring new hope. Methods: By searching the Surveillance, Epidemiology, and End Results database (SEER), 21,093 patients' clinical data were eventually included. Data were then divided into two groups (train dataset/test dataset). The train dataset (diagnosed in 2010-2014, N = 17,296) was utilized to conduct a deep learning survival model, validated by itself and the test dataset (diagnosed in 2015, N = 3,797) in parallel. According to clinical experience, age, sex, tumor site, T, N, M stage (7th American Joint Committee on Cancer TNM stage), tumor size, surgery, chemotherapy, radiotherapy, and history of malignancy were chosen as predictive clinical features. The C-index was the main indicator to evaluate model performance. Results: The predictive model had a 0.7181 C-index (95% confidence intervals, CIs, 0.7174-0.7187) in the train dataset and a 0.7208 C-index (95% CIs, 0.7202-0.7215) in the test dataset. These indicated that it had a reliable predictive value on OS for SCLC, so it was then packaged as a Windows software which is free for doctors, researchers, and patients to use. Conclusion: The interpretable deep learning survival predictive tool for small cell lung cancer developed by this study had a reliable predictive value on their overall survival. More biomarkers may help improve the prognostic predictive performance of small cell lung cancer.

Functional characterization and transcriptional activity analysis of Dryopteris fragrans farnesyl diphosphate synthase genes.

Farnesyl diphosphate synthase (FPS), a key enzyme of the terpene metabolic pathway, catalyzes the precursor of sesquiterpene compounds farnesyl diphosphate (FPP) synthesis, and plays an important role in regulating plant growth and development. Dryopteris fragrans is a medicinal plant rich terpenoids. In this study, the function of the gene was verified in vitro and in vivo, the promoter of the gene was amplified and its transcriptional activity was analyzed. In the present study, we report the molecular cloning and functional characterization of DfFPS1 and DfFPS2, two FPS genes from D. fragrans. We found that the two genes were evolutionarily conserved. Both DfFPS genes were highly expressed in the gametophyte and mature sporophyte leaves, and their expression levels increased in response to methyl jasmonate (MeJA) and high temperature. Both DfFPS proteins were localized in the cytoplasm and could catalyze FPP synthesis in vitro. We also found that the overexpression of DfFPS genes in tobacco plants promoted secondary metabolite accumulation but exhibited negligible effect on plant growth and development. However, the transgenic plants exhibited tolerance to high temperature and drought. The promoters of the two genes were amplified using fusion primer and nested integrated polymerase chain reaction (FPNI-PCR). The promoter sequences were truncated and their activity was examined using the ß-glucuronidase (GUS) gene reporter system in tobacco leaves, and we found that both genes were expressed in the stomata. The transcriptional activity of the promoters was found to be similar to the expression pattern of the genes, and the transcriptional core regions of the two genes were mainly between -943 bp and -740 bp of proDfFPS1. Therefore, we present a preliminary study on the function and transcriptional activity of the FPS genes of D. fragrans and provide a basis for the regulation of terpene metabolism in D. fragrans. The results also provide a novel basis for the elucidation of terpene metabolic pathways in ferns.

Research on wind farm participating in AGC based on wind power variogram characteristics.

The increasing integration of large-scale wind power aggravates the difficulty of maintaining system frequency deviations in a certain range. The frequency regulation pressure of conventional generators increases, which requires wind farms to participate in system frequency regulation. In this paper, a multi-area interconnected power system frequency response model with wind power is established. Based on the frequency response model, the state space model of regional interconnected power system is presented. Then, the wind power variogram characteristics are introduced for estimating wind power variations in different time-scales. By predicting the wind power variations in AGC time-scale, a strategy of wind farm participating in AGC system is proposed and performed based on model predictive control (MPC). The control strategy makes the conventional units and wind farms to participate in AGC system coordinately. Simulation results are provided which verifies the feasibility and validity of the proposed strategy.

Microfluidic Model to Mimic Initial Event of Neovascularization.

Neovascularization is usually initialized from an existing normal vasculature and the biomechanical microenvironment of endothelial cells (ECs) in the initial stage varies dramatically from the following process of neovascularization. Although there are plenty of models to simulate different stages of neovascularization, an in vitro 3D model that capitulates the initial process of neovascularization under the corresponding stimulations of normal vasculature microenvironments is still lacking. Here, we reconstructed an in vitro 3D model that mimics the initial event of neovascularization (MIEN). The MIEN model contains a microfluidic sprouting chip and an automatic control, highly efficient circulation system. A functional, perfusable microchannel coated with endothelium was formed and the process of sprouting was simulated in the microfluidic sprouting chip. The initially physiological microenvironment of neovascularization was recapitulated with the microfluidic control system, by which ECs would be exposed to high luminal shear stress, physiological transendothelial flow, and various vascular endothelial growth factor (VEGF) distributions simultaneously. The MIEN model can be readily applied to the study of neovascularization mechanism and holds a potential promise as a low-cost platform for drug screening and toxicology applications.

Flow shear stress controls the initiation of neovascularization via heparan sulfate proteoglycans within a biomimetic microfluidic model.

Endothelial cells (ECs) in vivo are subjected to three forms of shear stress induced by luminal blood flow, transendothelial flow and interstitial flow simultaneously. It is controversial that shear stress, especially the component induced by luminal flow, was thought to inhibit the initialization of angiogenesis and trigger arteriogenesis. Here, we combined microfabrication techniques and delicate numerical simulations to reconstruct the initial physiological microenvironment of neovascularization in vitro, where ECs experience high luminal shear stress, physiological transendothelial flow and various vascular endothelial growth factor (VEGF) distributions simultaneously. With the biomimetic microfluidic model, cell alignment and endothelial sprouting assays were carried out. We found that luminal shear stress inhibits endothelial sprouting and tubule formation in a dose-dependent manner. Although a high concentration of VEGF increases EC sprouting, neither a positive nor a negative VEGF gradient additionally affects the degree of sprouting, and luminal shear stress significantly attenuates neovascularization even in the presence of VEGF. Heparinase was used to selectively degrade the heparan sulfate proteoglycan (HSPG) coating on ECs and messenger RNA profiles in ECs were analyzed. It turned out that HSPGs could act as a mechanosensor to sense the change of fluid shear stress, modulate multiple EC gene expressions, and hence affect neovascularization. In summary, distraction from the stabilized state, such as decreased luminal shear stress, increased VEGF and the destructed mechanotransduction of HSPGs would induce the initiation of neovascularization. Our study highlights the key role of the magnitude and forms of shear stress in neovascularization.

[The clinical efficacy and cardiac safety of itraconazole injection in treatment of acute pulmonary invasive fungal infection in chronic pulmonary diseases in the elderly].

OBJECTIVE: To observe the clinical efficiency and cardiac safety of itraconazole injection in the treatment of the elderly patients with chronic pulmonary diseases suffered from acute pulmonary invasive fungal infection (IFI). METHODS: The research was single centre and open experimental designed trial. We selected patients (> 70 years old) who were admitted to our department of respiratory medicine because of chronic pulmonary diseases combined with pulmonary IFI. All patients received intravenous itraconazole injection. The clinical efficiency and cardiac safety was observed for 14 days. RESULTS: Thirty-five patients were included, 3 patients were proven, 32 patients were probable. There were 26 patients combined with coronary artery disease (74.28%), 20 patients combined with cor pulmonale (57.14%), and 17 patients simultaneously combined with both (48.57%). The temperature of 22 patients (62.86%) decreased to normal in 7 days, 31 patients (90.39%) in 11 days. After 14 days' therapy, the level of 1, 3-beta-D glucan decreased to normal in 26 patients (78.79%). The foci in sternum of 5 patients who were infected by candida albicans were completely absorbed in 14 days. Two patients were suffered from left heart insufficiency and arrhythmia ventricular on the 4th and 5th day respectively, and disappeared on the next day after given symptomatic treatment. There was a significant difference in B-type natriuretic peptide (BNP) between before and after treatment. CONCLUSION: The clinical efficiency of itraconazole injection in the elderly patients who suffered from chronic pulmonary diseases and then combined with acute pulmonary IFI were 78.79%. Even if combined with coronary artery disease and/or cor pulmonale, the elderly patients who have chronic pulmonary diseases were safe when using the itraconazole injection in 14 days.

The influence of an upgrade on the reduction of organophosphate flame retardants in a wastewater treatment plant.

The appearance of an increased amount of organophosphate flame retardant (OPFRs) in natural water is related the treated effluents from wastewater treatment plants (WWTPs) and thus understanding the OPFRs concentration and reduction variation in WWTPs would provide valuable insight into OPFR management and reduction. In this study, we have analyzed OPFRs (10 kinds: tris(chloroethyl) phosphate (TCEP), tris(2-chloroisopropyl) phosphate (TCPP), tris(1,3-dichloropropyl) phosphate (TDCP), tris(phenyl) phosphate (TPhP), tris(2-ethylhexyl) phosphate (TEHP), diphenylcresylphosphate (DCP), tris(methylphenyl) phosphate (TCP), tris(2-butoxyethyl) phosphate (TBEP), 2-ethylhexyl diphenyl phosphate (EHDP), and tris(butyl) phosphate (TBP)) in both water and sludge samples collected from different phases of a WWTP upgrading. The results show that TCPP and TCEP were mainly present in the aqueous phase, whereas TEHP dominated in the solid phase. The overall OPFR reduction efficiencies were above 40% through whole treatment processes by all the phases. More OPFRs reduction efficiency in primary sedimentation tanks was higher mainly because of bigger tank volume. The anaerobic zone in all cases could decrease OPFRs by over 13%. The removal of OPFRs in the oxic zone highly varied under the influence of the aeration pipe, water temperature, and aeration amount. Compared with chlorinated OPFRs, aryl and alkyl OPFRs were easier to reduce and less affected by the upgrading. Because OPFRs have been widely used in plastic materials such as pipes, WWTP upgrading - which usually requires more aeration and addition of reagents and instruments and the aim of which is normally to reduce more COD, N and P -- has introduced more OPFRs into the water within the WWTP.

Novel halos in light kaonic nuclei as an indicator of nuclear equation of state at supra-normal densities.

The sensitive correlations between the low-density halo structure and the high-density properties of the nuclear equation of state (EOS) are constructed in light kaonic nuclei with the relativistic mean-field theory. More specifically, the 1p 1/2 halo spreads out linearly with increasing the pressure and sound velocity square at supra-normal densities and decreasing the incompressibility at saturation density. These results suggest that the novel halo in light kaonic nuclei can serve as a sensitive indicator of the nuclear EOS of symmetric matter at supra-normal densities. The experimental production and detection of the light kaonic nuclei, yet to be available, is discussed in some details at last.

Signal transducers and activators of transcription 3 function in lung cancer.

Constitutively activation of signal transducers and activators of transcription 3 (STAT3) proteins are involved in multiple aberrant signaling pathway-oncogenic pathways, including pathways regulating tumor cell survival. STAT3 is one of the second messengers in the Janus activated family kinases/STAT signaling pathway and is regulated by many different factors involving tumorigenesis. Given that the activation of STAT3 is observed in nearly 50% of Lung cancers and more and more researches regarding STAT3 in tumors, here in, we reviewed the contribution of STAT3 to lung cancer growth and progression and then the context in which positive and negative regulation of STAT activation leading to cell competition provides a mechanism for therapeutic intervention for specific cancers is discussed.