Lung Cancer Progression Research Articles

Hsa_circ_0048764 facilitates the progression of non-small cell lung cancer by targeting miR-1178-3p/HMGA1 axis

Non-small cell lung cancer (NSCLC) remains a highly lethal disease, with a lack of fully established biomarkers and therapies. Circular RNAs (circRNAs) have emerged as powerful regulators of gene expression in multiple cancers. The role of circRNAs in NSCLC progression is still not well understood. In this study, GEO database analysis and qRT-PCR results revealed that hsa_circ_0048764 (circ_0048764) was overexpressed in NSCLC tissues and associated with poorer overall survival in patients with NSCLC. Functional assays demonstrated that silencing circ_0048764 inhibited NSCLC cell proliferation and metastasis. Bioinformatics analysis identified miR-1178-3p as having complementary binding sites with circ_0048764, a finding further validated by the dual-luciferase reporter assay. Additionally, predictions from the Starbase3.0 database, along with cellular experiments, revealed that miR-1178-3p regulates HMGA1 expression in NSCLC. Taken together, our findings suggest that circ_0048764 promotes NSCLC progression by enhancing HMGA1 expression through sponging miR-1178-3p, offering potential therapeutic targets for NSCLC treatment.

EP.13B.06 Efficacy and Safety Analysis of Atezolizumab Continuation Beyond Progression in Extensive Small Cell Lung Cancer(ES-SCLC)

EP.13B.06 Efficacy and Safety Analysis of Atezolizumab Continuation Beyond Progression in Extensive Small Cell Lung Cancer(ES-SCLC)

EP.04B.02 Identification of Circulating MicroRNAs Associated with Lung Cancer Diagnosis and Progression

EP.04B.02 Identification of Circulating MicroRNAs Associated with Lung Cancer Diagnosis and Progression

157 (PB145): Dietary sugar potentiates tobacco carcinogen-induced lung cancer development and progression by inducing the recruitment and protumoral polarization of macrophages

157 (PB145): Dietary sugar potentiates tobacco carcinogen-induced lung cancer development and progression by inducing the recruitment and protumoral polarization of macrophages

Retracted] lncRNA‑u50535 promotes the progression of lung cancer by activating CCL20/ERK signaling.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the western blotting data shown in Fig. 4B and C on p. 1952, and the Transwell invasion assay data in Fig. 2F and 4I, had already appeared in previously published articles written by different authors at different research institutes (a number of which have been retracted). Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 42: 1946‑1956, 2019; DOI: 10.3892/or.2019.7302].

BZW2 is a potential regulator of non-small cell lung cancer progression

BackgroundPersonalized targeted therapy has become an important strategy for cancer treatment owing to its remarkable therapeutic efficacy and safety. However, drug resistance remains the primary cause of treatment failure. Basic leucine zipper and W2 domain 2 (BZW2), which is aberrantly expressed in cancer, has been implicated in tumor progression and may serve as a new therapeutic target. Therefore, the role of BZW2 in non-small cell lung cancer (NSCLC) requires further investigation. MethodsThe expression and genetic alterations of BZW2 in pan-cancers were explored using The Cancer Genome Atlas (TCGA) PanCancer databases. The mRNA and protein levels of BZW2 in patients with NSCLC were verified in our cohort. Functional experiments including CCK8, colony formation, and transwell assays were performed to evaluate the impact of BZW2 on the proliferative, migratory, and invasive capacities of SK-MES-1 cells. Gene Set Enrichment Analysis was used to identify underlying biological processes and pathways. Single-cell RNA (scRNA) sequencing data were employed to investigate the tumor microenvironment of NSCLC and the co-expression of BZW2 and stemness-related genes. ResultsDysregulated BZW2 expression was observed in various malignant tumors. BZW2 expression was found to be significantly elevated in NSCLC. BZW2 depletion inhibited the growth, mobility, and invasive abilities of lung squamous cell carcinoma SK-MES-1 cells. BZW2 may be related to signaling pathways such as nucleotide excision repair, ubiquitin-mediated proteolysis, and the P53 signaling pathway. Biological processes, including translational initiation, tRNA processing, and RNA methylation, were observed to be enriched in the high-BZW2 group. Furthermore, there was a positive correlation between BZW2 and the m6A- and m5C-related genes. scRNA analysis revealed a co-expression relationship between BZW2 and stemness-related genes such as CD44, SOX9, and CD133. ConclusionsElevated BZW2 expression is associated with the proliferation, migration, and invasion of NSCLC, and BZW2 may be a potential therapeutic target for NSCLC.

Clofazimine inhibits small-cell lung cancer progression by modulating the kynurenine/aryl hydrocarbon receptor axis

Small cell lung cancer (SCLC) is one of the highly metastatic malignancies that contributes to ~15 % of all lung cancers. Most SCLC patients (50–60 %) develop osteolytic bone metastases, significantly affecting their quality of life. Among several factors, environmental pollutant 2,3,7,8-Tetrachlorodibenzodioxin (TCDD) and kynurenine (Kyn), an endogenous ligand derived from tryptophan (Trp) metabolism, activate the aryl hydrocarbon receptor (AhR) and are responsible for SCLC progression and metastasis. Further, elevated AhR expression in bone cells intensifies bone resorption, making the Kyn/AhR axis a potential target for the bone metastatic propensity of SCLC. We first assessed the expression profile of AhR in human SCLC cell lines and found a significantly increased expression compared to normal lung cells. Additionally, we also evaluated the clinical significance of AhR expression in the patient samples of SCLC along with the relevance of the same in the Rb1fl/fl; Trp53fl/fl; MycLSL/LSL (RPM) mouse model using immunohistochemistry and found the higher AhR expression in the patient samples and RPM mouse tumor tissues. Using computational simulations, we found that clofazimine (CLF) binds at the activator (Kyn) binding site by forming a stable complex with AhR. The CLF binding with AhR was favored by Van der Waals and hydrophobic forces, and the proteins retained their secondary structure. Furthermore, we found that Kyn treatment potentiates the migration and clonogenic ability of SCLC cell lines by activating Erk/Akt oncogenic signaling. Blocking AhR with CLF reduces AhR expression, inhibits Kyn-mediated proliferation of SCLC cells, and induces apoptosis and cell cycle arrest in the G2/M phase; further, our examination indicates that Kyn treatment also promotes osteoblast-mediated osteoclast differentiation through RANKL. The treatment with CLF impedes RANKL expression and osteoclastogenesis, suggesting that CLF has the potential for developing SCLC therapies that have efficacies against bone metastasis.

SOX4-BMI1 axis promotes non-small cell lung cancer progression and facilitates angiogenesis by suppressing ZNF24.

The incidence of lung cancer has become the highest among all cancer types globally, also standing as a leading cause of cancer-related deaths. Lung cancer is broadly divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with the latter accounting for 85% of total cases. SRY-box transcription factor 4 (SOX4), a crucial transcription factor, has been found to play a key role in the development of various cancers. However, the association between SOX4 and NSCLC is still unclear. This study investigated the clinical relevance of SOX4 and its potential mechanisms in the progression of NSCLC. Analysis of our NSCLC patient cohort revealed a significant increase in SOX4 levels in cancerous tissues, indicating its role as an independent prognostic indicator for NSCLC. In vitro experiments demonstrated that elevated SOX4 expression facilitated NSCLC cell migration, invasion, and EMT. Functionally, SOX4 drives NSCLC progression by enhancing the transcription and expression of B-cell-specific moloney leukemia virus insertion site 1 (BMI1). The oncogenic impact of SOX4-induced BMI1 expression on NSCLC advancement was validated through both in vivo and in vitro studies. In addition, our findings showed that BMI1 promoted the ubiquitination of histone H2A (H2Aub), leading to decreased zinc finger protein 24 (ZNF24) expression, which subsequently triggered vascular endothelial growth factor A (VEGF-A) secretion in NSCLC cells, thereby promoting NSCLC angiogenesis. Moreover, we evaluated the therapeutic potential of a BMI1 inhibitor in combination with Bevacizumab for NSCLC treatment using orthotopic models. The data presented in our study reveal a previously unrecognized role of the SOX4-BMI1 axis in promoting NSCLC progression and angiogenesis. This research significantly contributes to our knowledge of the interplay between SOX4 and BMI1 in NSCLC, potentially paving the way for the development of targeted therapies for this disease.

Impact of the Lung Microbiota on Development and Progression of Lung Cancer.

The past several years have provided a more profound understanding of the role of microbial species in the lung. The respiratory tract is a delicate ecosystem of bacteria, fungi, parasites, and viruses. Detecting microbial DNA, pathogen-associated molecular patterns (PAMPs), and metabolites in sputum is poised to revolutionize the early diagnosis of lung cancer. The longitudinal monitoring of the lung microbiome holds the potential to predict treatment response and side effects, enabling more personalized and effective treatment options. However, most studies into the lung microbiota have been observational and have not adequately considered the impact of dietary intake and air pollutants. This gap makes it challenging to establish a direct causal relationship between environmental exposure, changes in the composition of the microbiota, lung carcinogenesis, and tumor progression. A holistic understanding of the lung microbiota that considers both diet and air pollutants may pave the way to improved prevention and management strategies for lung cancer.

Enhancing Non-Small Cell Lung Cancer Survival Prediction through Multi-Omics Integration Using Graph Attention Network.

Background: Cancer survival prediction is vital in improving patients' prospects and recommending therapies. Understanding the molecular behavior of cancer can be enhanced through the integration of multi-omics data, including mRNA, miRNA, and DNA methylation data. In light of these multi-omics data, we proposed a graph attention network (GAT) model in this study to predict the survival of non-small cell lung cancer (NSCLC). Methods: The different omics data were obtained from The Cancer Genome Atlas (TCGA) and preprocessed and combined into a single dataset using the sample ID. We used the chi-square test to select the most significant features to be used in our model. We used the synthetic minority oversampling technique (SMOTE) to balance the dataset and the concordance index (C-index) to measure the performance of our model on different combinations of omics data. Results: Our model demonstrated superior performance, with the highest value of the C-index obtained when we used both mRNA and miRNA data. This demonstrates that the multi-omics approach could be effective in predicting survival. Further pathway analysis conducted with KEGG showed that our GAT model provided high weights to the features that are associated with the viral entry pathways, such as the Epstein-Barr virus and Influenza A pathways, which are involved in lung cancer development. From our findings, it can be observed that the proposed GAT model leads to a significantly improved prediction of survival by exploiting the strengths of multiple omics datasets and the findings from the enriched pathways. Our GAT model outperforms other state-of-the-art methods that are used for NSCLC prediction. Conclusions: In this study, we developed a new model for the survival prediction of NSCLC using the GAT based on multi-omics data. Our model showed outstanding predictive values, and the KEGG analysis of the selected significant features showed that they were implicated in pivotal biological processes underlying pathways such as Influenza A and the Epstein-Barr virus infection, which are linked to lung cancer progression.

Identification of hsa-miR-193a-5p-SURF4 axis related to the gut microbiota-metabolites- cytokines in lung cancer based on Mendelian randomization study and bioinformatics analysis

BackgroundLung cancer is a significant disease that affects people's physical and mental health. Currently, the treatment outcomes still do not meet clinical needs, and the causes of the disease are still unclear, therefore further exploration is needed.MethodsWe analyzed the exposure factors of lung cancer, including gut microbiota, serum metabolites, and cytokines, through Mendelian randomization studies and bioinformatics analysis. We identified common SNPs and performed gene annotation, leading to the discovery of the key gene SURF4, which may affect the onset of lung cancer. We validated the oncogenic function and mechanism of SURF4 through public data analysis using GO and KEGG, and constructed a ceRNA network, revealing the lung cancer oncogenic pathway involving lncRNA/pseudogene-microRNA-SURF4.ResultsWe first conducted a Mendelian randomization analysis on 418 gut microbiota, 1400 serum metabolites, and 41 cytokines in relation to lung cancer. We found that 16 gut microbiota, 29 serum metabolites, and 2 cytokines were closely associated with lung cancer. Further comparison of all differential SNPs revealed that rs550057 on chromosome 9 was a common SNP among these three exposure factors, indicating its crucial role in lung cancer formation. Through gene functional annotation using R language, we found that the expression of 15 genes, including SURF4, was influenced by rs550057. By querying these 15 genes from public databases for their differential expression and prognosis in lung cancer, we found significant differences in SURF4, MED22, and RPL7A. Furthermore, by querying the expression and correlation coefficients of upstream microRNAs of these three genes through the starBase website, we found that hsa-miR-193a-5p-SURF4 had the most significant effect on lung cancer. Through GO and KEGG analysis of SURF4-related genes, we identified the molecular pathways associated metabolic synthesis and microbial infection related to the promotion of lung cancer by SURF4. This validated the results of the previous Mendelian randomization study. Furthermore, we constructed a ceRNA network for SURF4 and identified two upstream differentially expressed pseudogenes and nine lncRNAs, confirming the functionality of the pseudogene/lncRNA-microRNA-SUFR4 pathway.ConclusionsIn summary, we have elucidated the regulatory role of the pseudogene/lncRNA-microRNA-SUFR4 pathway in the progression of lung cancer, combining the research hotspots of gut microbiota-serum metabolites-cytokines. We have also confirmed the pathway and mechanism through SURF4 and its related genes promoting lung cancer formation. This may provide effective therapeutic methods for lung cancer and serve as a potential prognostic marker.

USP5 promotes tumor progression by stabilizing SLUG in bladder cancer.

Bladder cancer ranks as the second most prevalent urology malignancy globally. Invasive metastasis is a significant contributor to mortality among patients with bladder cancer, yet the underlying mechanisms remain elusive. Deubiquitinases are pivotal in carcinogenesis, with USP5 implicated in the malignant progression of hepatocellular carcinoma, colorectal cancer and non-small cell lung cancer. The present study assessed the role and mechanism of ubiquitin-specific proteinase 5 (USP5) in the malignant progression of bladder cancer. The association between USP5 expression and bladder cancer prognosis and stage was analyzed using The Cancer Genome Atlas database. Moreover, to elucidate the role of USP5 in bladder cancer, USP5 overexpression and knockdown cell lines were established using T24 cells. Cell viability, proliferation and migration were assessed using Cell Counting Kit-8, Transwell and scratch assays, respectively. Cyclohexanamide was used to evaluate the effect of USP5 expression on Snail family zinc finger 2 (SLUG) stability. Immunoprecipitation and immunofluorescence co-localization were utilized to probe the interaction between USP5 and SLUG. Changes in mRNA and protein levels were assessed using reverse transcription-quantitative PCR and western blotting, respectively. The results revealed that patients with bladder cancer with high USP5 expression had significantly shorter survival (P<0.05) and a higher clinicopathologic stage (P<0.05) than those with low USP5 expression. T24 cells overexpressing USP5 demonstrated significantly increased proliferation (P<0.05), invasion (P<0.05) and expression of epithelial-mesenchymal transition markers (P<0.05); whereas T24 cells with knocked-down USP5 expression revealed significantly reduced proliferation (P<0.05), invasion (P<0.05) and epithelial-mesenchymal transition markers (P<0.05). Immunoprecipitation experiments demonstrated the binding of USP5 to SLUG in bladder cancer cells, with further analysis revealing that USP5 upregulated protein levels of SLUG by inhibiting its ubiquitination. Furthermore, the treatment of bladder cancer cells with Degrasyn, a USP5 inhibitor, was associated with a significant inhibition of the proliferation (P<0.05) and invasion (P<0.05) of T24 cells. In conclusion, the findings of the present study underscore the role of USP5 in promoting the malignant progression of bladder cancer through the stabilization of SLUG. Targeting USP5 holds promise as a strategy for inhibiting bladder cancer progression.

NSUN4-mediated m5C modification of circERI3 promotes lung cancer development by altering mitochondrial energy metabolism

As a highly important methylation modification, the 5-methyladenosine (m5C) modification can profoundly affect RNAs by regulating their transcription, structure and stability. With the continuous development of high-throughput technology, differentially expressed circular RNAs (circRNAs) have been increasingly discovered, and circRNAs play unique roles in tumorigenesis and development. However, the regulatory mechanism of the m5C modification of circRNAs has not yet been revealed. In this study, circERI3, which is highly expressed in lung cancer tissue and significantly correlated with the clinical progression of lung cancer, was initially identified through differential expression profiling of circRNAs. A combined m5C microarray analysis revealed that circERI3 contains the m5C modification and that the NSUN4-mediated m5C modification of circERI3 can increase its nuclear export. The important function of circERI3 in promoting lung cancer progression in vitro and in vivo was clarified. Moreover, we elucidated the novel mechanism by which circERI3 targets DNA binding protein 1 (DDB1), regulates its ubiquitination, enhances its stability, and in turn promotes the transcription of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) through DDB1 to affect mitochondrial function and energy metabolism, which ultimately promotes the development of lung cancer. This study not only revealed the reasons for the abnormal distribution of circERI3 in lung cancer tissues from the perspective of methylation and clarified the important role of circERI3 in lung cancer progression but also described a novel mechanism by which circERI3 promotes lung cancer development through mitochondrial energy metabolism, providing new insights for the study of circRNAs in lung cancer.

Histone variant H2AZ1 drives lung cancer progression through the RELA-HIF1A-EGFR signaling pathway

BackgroundA growing body of evidence indicates that histone variants play an oncogenic role in cancer progression. However, the role and mechanism of histone variant H2AZ1 in lung cancer remain poorly understood. In this study, we aim to identify novel functions and molecular mechanisms of H2AZ1 in lung cancer.MethodsWe analyzed H2AZ1 expression in lung adenocarcinoma using several RNA-seq and microarray datasets. Immunohistochemistry staining for H2AZ1 was performed on two sets of lung cancer tissue microarrays. To study the function of H2AZ1, we conducted assays for cell proliferation, colony formation, invasion, and migration. We employed CUT&Tag-seq, ATAC-seq, RNA-seq, and Western blotting to explore the regulatory patterns and potential mechanisms of H2AZ1 in lung adenocarcinoma.ResultsOur findings reveal that H2AZ1 is highly expressed in lung cancer and high levels of H2AZ1 mRNA are associated with poor patient survival. Silencing H2AZ1 impaired cell proliferation, colony formation, migration, and invasion. Mechanistically, our CUT&Tag-seq, ATAC-seq, and RNA-seq results showed that H2AZ1 is primarily deposited around TSS and affects multiple oncogenic signaling pathways. Importantly, we uncovered that H2AZ1 may drive lung cancer progression through the RELA-HIF1A-EGFR signaling pathway.ConclusionH2AZ1 plays an oncogenic role via several cancer-related pathways, including the RELA-HIF1A-EGFR axis in lung cancer. Intervention targeting H2AZ1 and its related signaling genes may have translational potential for precision therapy.

Cross-omics strategies and personalised options for lung cancer immunotherapy.

Lung cancer is one of the most common malignant tumours worldwide and its high mortality rate makes it a leading cause of cancer-related deaths. To address this daunting challenge, we need a comprehensive understanding of the pathogenesis and progression of lung cancer in order to adopt more effective therapeutic strategies. In this regard, integrating multi-omics data of the lung provides a highly promising avenue. Multi-omics approaches such as genomics, transcriptomics, proteomics, and metabolomics have become key tools in the study of lung cancer. The application of these methods not only helps to resolve the immunotherapeutic mechanisms of lung cancer, but also provides a theoretical basis for the development of personalised treatment plans. By integrating multi-omics, we have gained a more comprehensive understanding of the process of lung cancer development and progression, and discovered potential immunotherapy targets. This review summarises the studies on multi-omics and immunology in lung cancer, and explores the application of these studies in early diagnosis, treatment selection and prognostic assessment of lung cancer, with the aim of providing more personalised and effective treatment options for lung cancer patients.

Abstract C172: Diversifying translational research models to address outcomes disparities in lung cancer

Abstract Introduction: Racial disparities in lung cancer remains a persistent and challenging problem, with African Americans experiencing the highest mortality of any race or ethnic group. Emerging evidence suggests that multiple biological factors affect the development and progression of lung cancer. Three-dimensional organoid culture models have become important instruments to use for biomarker analysis and drug sensitivity screening. Despite this strong rationale and potential, there is a lack of representative preclinical models from African American patients with lung cancer. Furthermore, there are no studies evaluating the ability to create organoids successfully using samples from different races. As such, our goal was to establish a diverse biobank of organoid models and determine the rate of successful development based on race and other factors. Methods: Patients with lung cancer from a large urban medical center were recruited to participate in the study from 2021 to 2024. Specimens were collected from surgical pulmonary resection or endobronchial biopsy. Each tissue specimen was divided into 3 pieces and allocated for genomic, transcriptomic and organoid development. Once collected, specimens allocated for organoid development were processed within 8 hours. Cells were isolated from tissues by mechanical and enzymatic dissociation and plated in Matrigel drops overlayed with optimized organoid media. Patient demographics, tumor characteristics and method of specimen collection were recorded. Results: A total of 29 patients consented to the study and had evaluable specimens collected. Mean age was 67 years. Fifty-five percent of patients (16/29) were female. White patients were 55 percent of cohort (16/29), while Black patients made up 45% (13/29). Approximately 62 (18/29) percent of patients were diagnosed with adenocarcinoma, followed by squamous cell carcinoma in 28 percent (8/29) of patients. Tumor stage was 55%, 28%, 3% and 14% for stages I, II, III and IV respectively. Overall, there was a successful organoid development rate of 69 percent (20/29). There was a strong trend toward higher success rates in Black patients compared to White patients (85% vs. 56%, p = 0.10). There were no significant differences in successful organoid development based on gender (p = 0.43), histology (p = 0.18) or tumor stage (p = 0.84). Conclusions: Establishment of a racially diverse set of organoid models will be an invaluable tool for biomarker discovery and for screening novel therapeutic agents. Black patients appear to have similar to improved propensity for successful organoid development. Future efforts should be focused on creating diverse biobanks to strengthen precision oncology efforts for Black patients, collectively helping to reduce racial outcomes disparities in patients with lung cancer. Citation Format: Amanda Pilling, Hollis Hutchings, Avi Cohen, Shirish Gadgeel, Ikenna Okereke. Diversifying translational research models to address outcomes disparities in lung cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C172.

Fascin Inhibitor NP-G2-044 Decreases Cell Metastasis and Increases Overall Survival of Mice-Bearing Lung Cancers.

Fascin is an actin-binding protein that promotes tumor metastasis. The inhibition of fascin on the progress of non-small cell lung cancer (NSCLC) is not very clear. Hence, this study explored the potential effect of NP-G2-044, a novel fascin inhibitor, in human NSCLC lines and the Lewis lung cancer (LCC) mice model. The growth of cells was analyzed via CCK-8 assays, and the flow cytometry was adopted for cell cycle and apoptosis analysis, as well as the migration and invasion of NSCLC cells with or without NP-G2-044. The therapy of NP-G2-044, which synergizes with cisplatin and PD-1, was evaluated in the established xenograft Lewis's lung cancer of mice. Fascin was overexpressed in human NSCLC cells, and inhibition of fascin by NP-G2-044 attenuated NSCLC cell growth and remarkably undermined the ability of migration and invasion in vitro, which was related to the reduced epithelialmesenchymal transition (EMT) including downregulation of N-cadherin and vimentin, and upregulation of E-cadherin. Further results implied that the above changes may be partially mediated by the Wnt/β-catenin pathway. In vivo, NP-G2-044 slowed down tumor development and enhanced overall survival alone, leading to synergistic anticancer effects with cisplatin or PD-1 inhibitor. Fascin inhibition could inhibit the metastasis of NSCLC and has the potential to enhance the efficacy of cisplatin and PD-1 inhibitors by blocking the Wnt/β- catenin pathway.

PARD6A promotes lung adenocarcinoma cell proliferation and invasion through Serpina3.

Par6α encoded by PARD6A is a member of the PAR6 family and is reported to promote cancer initiation and progression. PARD6A is frequently upregulated in different types of cancers, but its regulatory role in lung cancer progression is yet to be established. In this study, we analyzed the PARD6A expression in biopsies from lung adenocarcinoma (LUAD) patients, and the survival probability using LUAD tissue microarray (TMA) and online datasets from TCGA and GEO. We conducted in vitro and in vivo assays to assess the role of PARD6A in regulating lung cancer progression, including proliferation, wound healing, transwell, RNA-seq, and subcutaneous tumor mice models. Our findings revealed that PARD6A is highly expressed in cancer tissues from LUAD patients and is associated with poor prognosis in LUAD patients. In vitro assays showed that PARD6A promoted cell proliferation, migration, and invasion. The transcriptome sequencing identified Serpina3 as one of the key downstream molecules of PARD6A. Ectopic expression of Serpina3 rescued impaired proliferation, migration, and invasion in PARD6A-knocking down H1299 cells, whereas silencing Serpina3 impeded enhanced proliferation, migration, and invasion in PARD6A-overexpressing H1975 cells. Our findings suggest that PARD6A promotes lung cancer progression by inducing Serpina3, which may be a promising therapeutic target.

Deciphering the role of claudins in lung cancer.

Lung cancer remains a major global health challenge, characterized by aggressive malignancy and poor prognostic outcomes. This review article focuses on the pivotal role of claudins, a family of tight junction proteins, in the pathophysiology of lung cancer. Claudins are integral to maintaining epithelial barrier function and cellular polarity, yet they are intricately involved in the progression and metastasis of lung cancer. The aberrant expression of claudins has been observed across various histological subtypes of lung cancer, indicating their potential as diagnostic and prognostic biomarkers. Specifically, claudins such as claudin-1, -2, -3, -4, and -7 exhibit diverse expression patterns that correlate with tumor aggressiveness, patient survival rates, and response to therapies. Inflammation and cytokine modulation significantly influence claudin expression, affecting tumor microenvironment dynamics and cancer progression. This review also highlights the therapeutic implications of targeting claudins, particularly in cases resistant to conventional treatments. Recent advances in this area suggest that claudin-modulating agents may enhance the efficacy of existing therapies and offer new avenues for targeted interventions. By integrating the latest research, this article aims to provide a comprehensive understanding of claudin's roles in lung cancer and encourages further clinical trials to explore claudin-targeting therapies. This could pave the way for more effective management strategies, improving outcomes for lung cancer patients.

Chronic stress promotes non-small cell lung cancer (NSCLC) progression through circMBOAT2 upregulation mediated by CTCF

Chronic stress promotes non-small cell lung cancer (NSCLC) progression through circMBOAT2 upregulation mediated by CTCF