Main Types Of Lung Cancer Research Articles

The suppression of OTUD7B by miR-491-5p enhances the ubiquitination of VEGFA to suppress vascular mimicry in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the main type of lung cancer with high morbidity and mortality. Vascular mimicry (VM), a distinct microcirculation model in tumors that differs from classical angiogenesis, is strongly associated with poor clinical outcomes in cancer patients. miR-491-5p has been reported to prevent NSCLC progression, including proliferation, metastasis, and angiogenesis. However, the effect and mechanism of miR-491-5p on VM have not been studied in NSCLC. The expression of miR-491-5p was detected by quantitative reverse transcription PCR (qPCR) and fluorescence in situ hybridization (FISH). Cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) staining assays were used to examine cell growth. Tube formation assay was used to assess VM in NSCLC cells. Immunohistochemistry (IHC) and western blot were performed to detect protein expression. Immunoprecipitation was used to confirm the interaction between OTU deubiquitinase 7B (OTUD7B) and vascular endothelial growth factor A (VEGFA), and the level of ubiquitinated VEGFA. A nude mouse tumorigenesis model was used to evaluate the carcinogenic capacity of NSCLC cells in vivo. Luciferase reporter assay was used to identify the potential target of miR-491-5p. MiR-491-5p was found downregulated in NSCLC tissues, and miR-491-5p deficiency was strongly associated with angiogenesis. miR-491-5p mimics suppressed cell viability, migration, and VM. Conversely, an inhibitor of miR-491-5p had the opposite effect. OTUD7B, a deubiquitinase, was identified as a downstream target of miR-491-5p. A luciferase reporter assay indicated that miR-491-5p directly binds to the 3'UTR of OTUD7B. Moreover, mimics of miR-491-5p caused a significant reduction in the OTUD7B protein in NSCLC cells, and an inhibitor of miR-491-5p stabilized the OTUD7B protein. In addition, overexpression of OTUD7B promoted cell proliferation, migration, and VM, similar to the effects of an inhibitor of miR-491-5p. Further exploration revealed that OTUD7B interacts with VEGFA and that the miR-491-5p-OTUD7B axis modulates the ubiquitination of VEGFA. The rescue experiment indicated that OTUD7B compromised the inhibitory effects of miR-491-5p on the cellular function of NSCLC cells. Overall, our study first proved that miR-491-5p impedes VM by suppressing OUTD7B and promoting the ubiquitination of VEGFA. The miR-491-5p/OTUD7B axis may be a novel target for antiangiogenic therapy in NSCLC.

Isotoosendanin exerts anti-tumor effects in NSCLC by enhancing the stability of SHP-2 and inhibiting the JAK/STAT3 pathway

Lung cancer has been considered as a serious problem for the public health system. NSCLC is the main type of lung cancer, and finding improved treatments for NSCLC is a pressing concern. In this study, we have explored the efficacy of isotoosendanin (ITSN) for the treatment of NSCLC, and also explored the potential underlying mechanisms. NSCLC cells were cultured, and colony formation, cell cycle as well as apoptosis assays have been conducted for investigating the biological functions of ITSN on NSCLC cells. Furthermore, target genes of ITSN have been predicted via PharmMapper and SuperPred database, subsequently validated using the drug affinity responsive target stability (DARTS) approach, a cellular thermal shift assay (CETSA) as well as surface plasmon resonance (SPR) analysis. Additionally, ubiquitination experiments have been conducted for the level of ubiquitination of the NSCLC cells. Finally, a nude mouse xenograft model has been established for evaluating the anti-tumor effects of ITSN in vivo. ITSN has shown anti-NSCLC activities both in vitro and in vivo. Mechanistically, ITSN interacts with SHP-2 through enhancing its stability and decreases the level of ubiquitination. Notably, ITSN may regulate the behaviors of NSCLC cells via affecting the JAK/STAT3 signaling, and finally, the anti-tumor effects of ITSN was partially reversed by the application of SHP-2 inhibitor or siRNA of SHP-2. ITSN may exert its anti-tumor effects by directly targeting SHP-2, increasing its stability and minimizing its ubiquitination. These results imply that ITSN could be a revolutionary component for treating NSCLC.

25-hydroxycholesterol promotes proliferation and metastasis of lung adenocarcinoma cells by regulating ERβ/TNFRSF17 axis.

Lung adenocarcinoma is the main type of lung cancer in women. Our previous findings have evidenced that 25-hydroxycholesterol (25-HC) promotes migration and invasion of lung adenocarcinoma cells (LAC), during which LXR as a 25-HC receptor plays an important role. Estrogen receptor beta (ERβ) is a receptor of 27-hydroxycholesterol that is structurally analogous to 25-HC, but its role in the functional actions of 25-HC remained largely unknown. In this study, we demonstrated that 25-HC treatment triggered ERβ expression in LAC. Knockdown of ERβ inhibited 25-HC-mediated proliferation, migration and invasion, and reduced 25-HC-induced LAC metastasis in vivo. Further investigation revealed that ERβ knockdown restrained the expression of TNFRSF17 (BCMA). In vivo experiments also confirmed that ERβ knockdown blocked 25-HC-induced TNFRSF17 expression. TNFRSF17 knockdown also restrained 25-HC-induced proliferation, migration and invasion. Bioinformatic analysis showed that the levels of ERβ and TNFRSF17 were elevated in lung adenocarcinoma, and were closely related to tumor stages and nodal metastasis status. These results suggested that 25-HC promoted the proliferation and metastasis of LAC by regulating ERβ/TNFRSF17 axis.

Circ-NUP98 Promotes Lung Adenocarcinoma Development Through Regulating CBX1 by miR-188-3p.

Lung cancer has a high morbidity and mortality among malignant tumors, and lung adenocarcinoma (LUAD) is the main type of lung cancer. In recent years, circular RNAs (circRNAs) have been confirmed to play an important role in the generation and development of human cancer. However, the specific role and mechanism of circ-NUP98 in LUAD are still unclear and need to be further investigated. Circ-NUP98, microRNA-188-3p (miR-188-3p), and chromoboxhomolog1(CBX1)levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell-counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, wound healing, and transwell assay were used to observe LUAD cell proliferation, apoptosis, migration, invasion, and cell-cycle progression. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were examined using special assay kits. CyclinD1, Bcl-2-related X protein (Bax), matrix metalloproteinase 9 (MMP9) protein, and CBX1 protein levels were determined using Western blot. The interaction between miR-188-3p and circ-NUP98 or CBX1 was identified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assay. In vivo efficacy of circ-NUP98 was evaluated in a xenograft tumor model. Besides, the expression of CBX1 and KI67 in the tumors was detected by immunohistochemical (IHC) assay. Circ-NUP98 and CBX1 expressions were upregulated in LUAD tissues and cells, and miR-188-3p was decreased. Downregulation of circ-NUP98 could inhibit the proliferation, migration, invasion, and oxidative stress, and promote apoptosis of LUAD cells. Mechanism experiments showed that circ-NUP98 acted as a sponge for miR-188-3p to increase CBX1 expression. Knockdown of circ-NUP98 could inhibit the growth of LUAD tumors in vivo. Circ-NUP98 might promote the malignant development of LUAD via the miR-188-3p/CBX1 axis, which might provide a potential new marker for early diagnosis of LUAD.

Overview of Lung Cancer

The two main types of lung cancer are small cell carcinoma and non-small cell carcinoma. Lung cancer is a primary bronchogenic carcinoma. Patients who are diagnosed with lung cancer typically exhibit symptoms like hemoptysis, dyspnea, chronic cough, chest pain, or weight loss. Since the onset of symptoms typically indicates that a patient's stage has already progressed, screening with low-dose chest CT (LDCT) exams is advised for high-risk patients. Cytology and core biopsy specimens are the main sources of the diagnosis for these patients. Staging, histology, genetic, and immunotherapy biomarker tests form the basis of the treatment. The most often used pharmacological therapies include radiotherapy, adjuvant platinum-based chemotherapy, surgery, which might involve mediastinal lymph node dissection or lymph node sampling, as well as total removal of the tumor (typically stages I and II). Currently, meanwhile, immunotherapy is the most advanced form of treatment for NSCLC that is oncogenic driver negative

TMSB4X: A novel prognostic marker for non-small cell lung cancer

Non-small cell lung cancer (NSCLC), as the main type of lung cancer, has a long history of high incidence and mortality. Despite the continuous updates to the American Joint Committee on Cancer (AJCC) staging system, which adapt to evolving treatment modalities and diagnostic advancements, it is evident that patients at the same stage exhibit varying prognoses. The heterogeneity of tumors underscores the need for molecular diagnostics to assume a pivotal role in tumor staging and patient stratification. In our investigation, we meticulously analyzed the data of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, incorporating clinical patients and scrutinizing pathological specimens. Through this comprehensive approach, we established a correlation between the expression of the Thymosin beta 4 X-linked (TMSB4X) gene and poorer disease-free survival (DFS) and overall survival (OS) post-surgery. Compared to the TMSB4X positive expression group, patients in the negative expression group had a better prognosis, with longer DFS (median disease-free survival (median DFS): 16.2 months vs. 11.3 months, P = 0.032) and OS (median overall survival (mOS): 29.8 months vs. 18.5 months, P = 0.033). Furthermore, our findings suggest that TMSB4X may facilitate immune evasion in non-small cell lung cancer cells by influencing the activation of infiltrating dendritic cells (DCs) in tumor infiltrating immune cells (TIICs) (R = 0.27, P = 4.8E+08). In summary, TMSB4X emerges as an unfavorable prognostic factor for NSCLC, potentially modulating the tumor immune microenvironment through its regulatory impact on dendritic cell function, thus facilitating tumor immune escape.

Exploring the Role of DKK1 in the Occurrence of Lung Adenocarcinoma Based on the Analysis of Bioinformatics

Lung cancer is the most common malignant tumor in China, lung adenocarcinoma (LUAD) is the main type of lung cancer, which is a serious threat to people's life and health. At present, there are fewer studies on the role of Dikkopf1 (DKK1) in lung adenocarcinoma. The aim of this study was to investigate the role and potential prognostic value of DKK1 in the development of lung adenocarcinoma by bioinformatics methods. Several databases, such as genotype-tissue expression (GTEx), The Cancer Genome Atlas (TCGA) and tumor-immune system interactions database (TISIDB), were used to analyze the expression, clinicopathological features, immune cell infiltration, prognosis and methylation of DKK1 in lung adenocarcinoma. Then, linked immune cell infiltration Omics database was used to analyze the co-expressed genes of DKK1 and their functional enrichment. Finally, 59 pathological samples of paraffin-embedded lung adenocarcinoma patients who underwent surgery at the Affiliated Cancer Hospital of Xinjiang Medical University between 2016 and 2017 were collected for the validation of the prognostic value of expression by immunohistochemistry (IHC) test. The results of bioconfidence analysis showed that the expression level of DKK1 in lung adenocarcinoma tissues was higher than that in normal tissues, the expression in advanced cancers was higher than that in early stages, and the experimental validation revealed that among 59 cases of lung adenocarcinoma, there were 15 cases of negative expression (25.4%), 18 cases of weakly positive expression (30.5%), and 26 cases of strongly positive expression (44.1%). The different expression of DKK1 is related to methylation, prognosis and the activities of various immune cells. Functional enrichment shows that DKK1 may be involved in skin development and cell-substrate junction, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis shows that DKK1 is related to ABC transporters. Bioinformatics analysis and clinical case specimens showed that high DKK1 expression was associated with poorer prognosis in patients with lung adenocarcinoma. High expression of DKK1 in lung adenocarcinoma is associated with poor prognosis. DKK1 is closely associated with tumor immune cell infiltration and pathways. DKK1 can be considered as a potential prognostic marker and a novel target for immunotherapy of lung adenocarcinoma.

Integrative analysis of GWAS and transcriptomics data reveal key genes for non-small lung cancer.

Lung cancer is one of the world's most common and deadly cancers. The two main types of lung cancer are non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). More than 85% of lung cancers are NSCLC. Genetic factors play a significant role in the risk of NSCLC. Growing studies focus on studying risk factors at the molecular level. The aim of the study is to build a pipeline to integrate Genome-wide association analysis (GWAS) and transcriptomics data with machine learning to effectively identify genetic risk factors of NSCLC. GWAS datasets and GWAS summary data were downloaded from GWAS catalog, which include lung carcinoma genetic variants among the European population. Then, with the GWAS summary, data functional analysis of significant SNPs was performed using a webserver called FUMAGWAS. The transcriptomics data of NSCLC and non-NSCLC people were used to build a machine learning model to identify the key genes that help predict the NSCLC. The top up-regulation and down-regulation genes were identified by the BART cancer webserver, and the mechanistic roles of the genes were validated by literature review. By performing integrative analysis of GWAS and transcriptomics analysis using machine learning, we identified multiple SNPs and genes that related to NSCLC. The computational pipeline may facilitate the biomarker discovery for NSCLC and other diseases.

Bioinformatics analysis and in vivo validation study of Ophiocordyceps sinensis (Berk.)G.H.Sungetal against lung adenocarcinoma

Ethnopharmacological relevanceLung adenocarcinoma (LUAD) is one of the main types of lung cancer. Ophiocordyceps sinensis has many potentially useful pharmacologic features, such as lung protection, and both anti-inflammatory and antioxidant activities. Aim of the studyThis study was conducted to investigate—using bioinformatics and in vivo experimental validation—the possible role of O. sinensis against LUAD. Materials and methodsWe obtained important targets of O. sinensis for the treatment of LUAD using network pharmacology techniques and deep mining of the TCGA database, and validated them by molecular docking techniques and in vivo experiments. ResultsThrough bioinformatics analysis and research, we screened BRCA1 and CCNE1 as important biomarkers for LUAD and as core targets of O. sinensis against LUAD. The non-small cell lung cancer signaling pathway, PI3K-Akt signaling pathway, and HIF-1 signaling pathway are potentially important pathways of O. sinensis against LUAD. The molecular docking results showed good binding between the active components in O. sinensis and the two core targets, and the in vivo experimental validation results indicated that O. sinensis had good inhibitory effects in the Lewis lung cancer (LLC) model. ConclusionsBRCA1 and CCNE1 are crucial biomarkers for LUAD and are important targets for O. sinensis to exert anti-LUAD effects.

Berberine targets KIF20A and CCNE2 to inhibit the progression of nonsmall cell lung cancer via the PI3K/AKT pathway.

Nonsmall cell lung cancer (NSCLC) is the main type of lung cancer, accounting for approximately 85%. Berberine (BBR), a commonly used traditional Chinese medicine, has been reported to exhibit a potential antitumor effect in various cancers. In this research, we explored the function of BBR and its underlying mechanisms in the development of NSCLC. Cell Counting Kit-8 (CCK-8), 5-ethynyl-20-deoxyuridine (EdU), colony formation assays, flow cytometry, and transwell invasion assay were employed to determine cell growth, the apoptotic rate, cell invasion of NSCLC cells, respectively. Western blot was applied for detecting the protein expression of c-Myc, matrix metalloprotease 9 (MMP9), kinesin family member 20A (KIF20A), cyclin E2 (CCNE2), and phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway-related proteins. Glycolysis was evaluated by detecting glucose consumption, lactate production, and adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio with the matched kits. Real-time quantitative polymerasechain reaction(RT-qPCR) was conducted to analyze the level of KIF20A and CCNE2. Tumor model was established to evaluate the function of BBR on tumor growth in NSCLC in vivo. In addition, immunohistochemistry assay was employed to detect the level of KIF20A, CCNE2, c-Myc, and MMP9 in mice tissues. BBR exhibited suppressive effects on the progression of NSCLC, as evidenced by inhibiting cell growth, invasion, glycolysis, and facilitating cell apoptosis in H1299 and A549 cells. KIF20A and CCNE2 were upregulated in NSCLC tissues and cells. Moreover, BBR treatment significantly decreased the expression of KIF20A and CCNE2. KIF20A or CCNE2 downregulation could repress cell proliferation, invasion, glycolysis, and induce cell apoptosis in both H1299 and A549 cells. The inhibition effects of BBR treatment on cell proliferation, invasion, glycolysis, and promotion effect on cell apoptosis were rescued by KIF20A or CCNE2 overexpression in NSCLC cells. The inactivation of PI3K/AKT pathway caused by BBR treatment in H1299 and A549 cells was restored by KIF20A or CCNE2 upregulation. In vivo experiments also demonstrated that BBR treatment could repress tumor growth by regulating KIF20A and CCNE2 and inactivating the PI3K/AKT pathway. BBR treatment showed the suppressive impact on the progression of NSCLC by targeting KIF20A and CCNE2, thereby inhibiting the activation of the PI3K/AKT pathway.

Minimum Sample Size Estimate for Classifying Invasive Lung Adenocarcinoma

Statistical Learning Theory (SLT) plays an important role in prediction estimation and machine learning when only limited samples are available. At present, determining how many samples are necessary under given circumstances for prediction accuracy is still an unknown. In this paper, the medical diagnosis on lung cancer is taken as an example to solve the problem. Invasive adenocarcinoma (IA) is a main type of lung cancer, often presented as ground glass nodules (GGNs) in patient’s CT images. Accurately discriminating IA from non-IA based on GGNs has important implications for taking the right approach to treatment and cure. Support Vector Machine (SVM) is an SLT application and is used to classify GGNs, wherein the interrelation between the generalization and the lower bound of necessary sampling numbers can be effectively recovered. In this research, to validate the interrelation, 436 GGNs were collected and labeled using surgical pathology. Then, a feature vector was constructed for each GGN sample through the fully connected layer of AlexNet. A 10-dimensional feature subset was then selected with the p-value calculated using Analysis of Variance (ANOVA). Finally, four sets with different sample sizes were used to construct an SVM classifier. Experiments show that a theoretical estimate of minimum sample size is consistent with actual values, and the lower bound on sample size can be solved under various generalization requirements.

Evaluation of folate levels in patients of lung carcinoma

Introduction: Lung cancer is the leading cause of cancer death globally. It is the malignant lung tumor with numerous histological variants. Due to the increasing number of tobacco smoking it is the major risk factor for lung cancer. Two main types of Lung cancer are Non-Small cell lung carcinoma (NSCLC) and Small cell lung carcinoma (SCLC). Folate is a water-soluble natural form of vitamin B9. It plays important role in homocysteine metabolism. Its decreased level may be associated with various cancers as is linked with altered DNA methylation and synthesis, and disruption of DNA repair activities. Aims: The present study was planned to evaluate the Serum Folate levels in patients diagnosed with lung carcinoma and to explore the association of increased serum folate levels with lung carcinoma patients. Materials & Methods: Fifty patients diagnosed for lung carcinoma were enrolled according to the inclusion criteria for the study. Fifty age and sex matched healthy individuals constituted the control group. Serum folate levels were estimated for all enrolled subjects. Results obtained were compared statistically among the lung carcinoma and healthy control groups. Results: Age of the study group and control group were comparable.

27-hydroxycholesterol linked high cholesterol diet to lung adenocarcinoma metastasis.

Dietary cholesterol has been implicated to promote lung cancer. Lung adenocarcinoma (LAC) is a main type of lung cancer, whereas the functional mechanism of cholesterol in LAC remained largely unknown. In the present study, we evidenced that cholesterol promoted cell proliferation and invasion of LAC in vitro as well as LAC metastasis in vivo. Cyp27A1 knockdown reduced the cholesterol-induced LAC cells proliferation and invasion. In contrast, Cyp7B1 knockdown enhanced the effect of cholesterol on LAC cells proliferation and invasion. Furthermore, Cyp27A1 deficiency remarkably reduced high cholesterol-induced LAC metastasis in vivo. Mechanism investigation demonstrated that exposure of LAC cells to 27-hydroxycholesterol induced the phosphorylation of AKT and NFκB p65, and promoted the expression of peptidylprolyl isomerase B (PPIB), especially in the coculture with THP1-derived macrophage. Meanwhile, 27-hydroxycholesterol induced the secretion of FGF2 and IL-6, which contributed to the expression of snail and vimentin. Luciferase report assay and ChIP assay confirmed that NFκB p65 controlled the transcription of PPIB. Inhibiting NFκB p65 activation reduced PPIB expression. PPIB inhibition reduced 27-hydroxycholesterol-induced expression of snail and vimentin. These results indicated that 27-hydroxycholesterol linked high cholesterol and LAC metastasis by regulating NFκB/PPIB axis and the secretion of FGF2 and IL-6.

Electrochemical detection of ctDNA mutation in non-small cell lung cancer based on CRISPR/Cas12a system

Lung cancer is the leading cause of cancer-related death around the world. The circulating tumor DNA (ctDNA) of EGFR L858R in plasma is crucial for development, targeted drug therapy, and prognosis of non-small cell lung cancer, the main type of lung cancer. Accurately detecting ctDNA using conventional methods is challenging due to its characteristics, such as considerably short size, extremely low level, and short half-life. Thus, developing a rapid, accurate, and cost-effective method for ctDNA EGFR L858R detection is urgently needed. Herein, we developed an electrochemical biosensor of ctDNA EGFR L858R based on the CRISPR/Cas12a system and MB/Fe3O4@COF/PdAu nanocomposites. The CRISPR/Cas12a system played roles in the precise recognition of ctDNA targets and indistinguishable cleavage of single-stranded DNA. Additionally, the MB/Fe3O4@COF/PdAu nanocomposite has good catalytic activity and signal amplification performance. The proposed electrochemical biosensor showed high specificity, stability, and selectivity. Notably, the limit of detection of the proposed biosensor was 3.3 aM. The detection results of 25 clinical samples showed that 22 and 20 positive samples were detected by electrochemical detection and droplet digital polymerase chain reaction, respectively. Therefore, we established a high-precision, reliable, and convenient method for ctDNA detection, which has a potential application in the diagnosis and prognosis of cancer.

Combined metabolomics with transcriptomics reveals potential plasma biomarkers correlated with non-small-cell lung cancer proliferation through the Akt pathway

BackgroundNon-small-cell lung cancer (NSCLC) is one of the main types of lung cancer. Due to lack of effective biomarkers for early detection of NSCLC, the therapeutic effect is not ideal. This study aims to reveal potential biomarkers for clinical diagnosis. MethodsThe plasma metabolic profiles of the patients were characterized by liquid chromatography-mass spectrometry (LC-MS). Differential metabolites were screened by p less than 0.05 and VIP greater than 1. Multivariate statistical analysis was used to search for potential biomarkers. Receiver operating characteristic (ROC) curve was used to evaluate the predictors of potential biomarkers. Pathway enrichment analysis was performed on metabolomics data by Ingenuity Pathway Analysis (IPA) and transcriptomics data from GEO were used for validation. ResultsA plasma metabolite biomarker panel including 13(S)-hydroxyoctadecadienoic acid (13(S)-HODE) and arachidonic acid was chose. The area under the ROC curve were 0.917, 0.900 and 0.867 for the panel in the different algorithm like Partial Least Squares Discrimination Analysis (PLS-DA), Support Vector Machine (SVM), Random Forest (RF). The candidate biomarkers were associated with the Akt pathway. Genes involved in the biological pathway had significant changes in the expression levels. Conclusion13(S)-HODE and arachidonic acid may be potential biomarkers of NSCLC. The Akt pathway was associated with this biomarker panel in NSCLC. Further studies are needed to clarify the mechanisms of disruption in this pathway.

Traditional Herbal Medicine: A Potential Therapeutic Approach for Adjuvant Treatment of Non-small Cell Lung Cancer in the Future.

Lung carcinoma is the primary reason for cancer-associated mortality, and it exhibits the highest mortality and incidence in developed and developing countries. Non-small cell lung cancer (NSCLC) and SCLC are the 2 main types of lung cancer, with NSCLC contributing to 85% of all lung carcinoma cases. Conventional treatment mainly involves surgery, chemoradiotherapy, and immunotherapy, but has a dismal prognosis for many patients. Therefore, identifying an effective adjuvant therapy is urgent. Historically, traditional herbal medicine has been an essential part of complementary and alternative medicine, due to its numerous targets, few side effects and substantial therapeutic benefits. In China and other East Asian countries, traditional herbal medicine is increasingly popular, and is highly accepted by patients as a clinical adjuvant therapy. Numerous studies have reported that herbal extracts and prescription medications are effective at combating tumors. It emphasizes that, by mainly regulating the P13K/AKT signaling pathway, the Wnt signaling pathway, and the NF-κB signaling pathway, herbal medicine induces apoptosis and inhibits the proliferation and migration of tumor cells. The present review discusses the anti-NSCLC mechanisms of herbal medicines and provides options for future adjuvant therapy in patients with NSCLC.

Research Progress in CircRNA and Radiotherapy Resistance of Non-small Cell Lung Cancer

非小细胞肺癌（non-small cell lung cancer, NSCLC）作为临床上较为常见的癌症，主要特点是患者5年生存率低、预后偏差。目前有部分研究认为生存率低、预后偏差是由于环状RNA（circluar RNA, circRNA）引起了放疗抵抗。因此，找出circRNA与NSCLC放疗抵抗之间的联系，可为改善临床治疗提供理论基础。通过查阅相关文献，找出circRNA与NSCLC放疗抵抗的关系。CircRNA在NSCLC细胞的侵袭、转移、增殖和治疗抵抗中起着重要的作用，其中它所诱导的肿瘤细胞放疗抵抗已经成为放射治疗上的一个重点关注问题。CircRNA在NSCLC的放疗抵抗中起着重要作用。

Mufangji Decoction and Its Active Ingredient Patchouli Alcohol Inhibit Tumor Growth through Regulating Akt/mTOR-Mediated Autophagy in Nonsmall-Cell Lung Cancer.

Background Nonsmall-cell lung cancer (NSCLC) is the main type of lung cancer, whose morbidity and mortality rank first among malignant tumors. More than 70% of NSCLC patients are diagnosed at locally advanced or advanced stage, missing the best operation period. Chemotherapy and targeted therapy are important means for the treatment of advanced NSCLC, but various side effects seriously affect the curative effect and the life quality of NSCLC patients. Our previous clinical practice has shown that Mufangji Decoction, a classic traditional Chinese medicine, has a significant curative effect in the treatment of NSCLC, but the specific mechanism is not clear. This study intends to explore the potential mechanism of Mufangji Decoction and its active ingredient patchouli alcohol against NSCLC and to provide a scientific basis for the prevention and treatment of NSCLC by traditional Chinese medicine. Methods The in vivo and in vitro experiments were performed to evaluate the antitumor effects and investigate the underlying mechanism of Mufangji Decoction and its active ingredient patchouli alcohol. Network pharmacology was applied to analyze the effective ingredients and potential targets or signaling pathways of Mufangji Decoction. Results Our current study shows that Mufangji Decoction can effectively inhibit the growth of subcutaneous transplantation of NSCLC. The following network pharmacological analysis and in vivo experiment suggest that patchouli alcohol is one of the main active ingredients of Mufangji Decoction and exerts antitumor effects. Further mechanism investigation reveals that the antitumor effect of patchouli alcohol is related to the induction of Akt/mTOR signaling pathway-mediated autophagy in NSCLC cells. Conclusion Mufangji Decoction and its active ingredient patchouli alcohol might exert their antitumor effects in NSCLC partly through regulating Akt/mTOR-mediated autophagy, providing the evidence that traditional Chinese medicine might be a key approach for NSCLC treatment via targeting the Akt/mTOR signal axis.

Identification of a glycolysis-related gene signature associated with clinical outcome for patients with lung squamous cell carcinoma.

BackgroundLung squamous cell carcinoma (LUSC), one of the main types of lung cancer, has caused a huge social burden. There has been no significant progress in its therapy in recent years, Resulting in a poor prognosis. This study aims to develop a glycolysis‐related gene signature to predict patients’ survival with LUSC and explore new therapeutic targets.MethodsWe obtained the mRNA expression and clinical information of 550 patients with LUSC from the Cancer Genome Atlas (TCGA) database. Glycolysis genes were identified by Gene Set Enrichment Analysis (GSEA). The glycolysis‐related gene signature was established using the Cox regression analysis.ResultsWe developed five glycolysis‐related genes signature (HKDC1, AGL, ALDH7A1, SLC16A3, and MIOX) to calculate each patient's risk score. According to the risk score, patients were divided into high‐ and low‐risk groups and exhibited significant differences in overall survival (OS) between the two groups. The ROC curves showed that the AUC was 0.707 for the training cohort and 0.651 for the validation cohort. Additionally, the risk score was confirmed as an independent risk factor for LUSC patients by Cox regression analysis.ConclusionWe built a gene signature to clarify the connection between glycolysis and LUSC. This model performs well in evaluating patients’ survival with LUSC and provides new biomarkers for targeted therapy.

TP53-Activated lncRNA GHRLOS Regulates Cell Proliferation, Invasion, and Apoptosis of Non-Small Cell Lung Cancer by Modulating the miR-346/APC Axis.

Non-small cell lung cancer (NSCLC) is the main type of lung cancer with high mortality worldwide. To improve NSCLC therapy, the exploration of molecular mechanisms involved in NSCLC progression and identification of their potential therapy targeting is important. Long noncoding RNAs (lncRNAs) have shown important roles in regulating various tumors progression, including NSCLC. We found lncRNA GHRLOS was decreased in NSCLC cell lines and tissues which correlated with poor prognosis of NSCLC patients. However, the role and underlying mechanisms of lncRNA GHRLOS in NSCLC progression remains elusive. The expression of lncRNA GHRLOS was examined in NSCLC cell lines and biopsy specimens of patients with NSCLC by quantitative real time polymerase chain reaction (qRT-PCR). The effects of GHRLOS on proliferation, invasion and apoptosis of NSCLC cells were determined by both in vitro and in vivo experiments. The interaction between GHRLOS and TP53 was determined by dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) combined with qRT-PCR analysis. RNA immunoprecipitation (RIP) was conducted to validate the binding between GHRLOS and microRNA-346 (miR-346). Dual-luciferase reporter assays were also carried out to reveal the interaction between miR-346 and the 3’ untranslated region (3’UTR) of adenomatous polyposis coli (APC) mRNA.Our data demonstrated that overexpression of lncRNA GHRLOS suppressed cancer cell proliferation and invasion as well as promoted cell apoptosis by regulating the expression of CDK2, PCNA, E-cadherin, N-cadherin, Bax, and Bcl-2 in NSCLC cells. Moreover, lncRNA GHRLOS was upregulated by the binding of TP53 to the GHRLOS promoter. The binding target of lncRNA GHRLOS was identified to be miR-346. Impressively, overexpression of miR-346 promoted cell proliferation and invasion, as well as inhibited cell apoptosis, however, these effects can be blocked by overexpression of lncRNA GHRLOS both in vitro and in vivo. In summary, this study reveals lncRNA GHRLOS, upregulated by TP53, acts as a molecule sponge of miR-346 to cooperatively modulates expression of APC, a miR-346 target, and potentially inhibits NSCLC progression via TP53/lncRNA GHRLOS/miR-346/APC axis, which represents a novel pathway that could be useful in targeted therapy against NSCLC.