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ObjectivesCircular RNAs (circRNAs) are a class of non-coding RNAs with diverse pathophysiological functions. However, the functional roles and molecular mechanisms of circRNAs in lung adenocarcinoma (LUAD) remain to be further elucidated.MethodsThe expression levels of Circ₀007552 (Circ_(R)ILPL1), miR-7974, and BRCA1-associated protein 1 (BAP1) mRNA in LUAD tissues and cells were detected by quantitative real-time PCR (qRT-PCR). Cell viability, migration, and invasion capabilities were evaluated using the Cell Counting Kit-8 (CCK-8), colony formation assay, wound healing assay, and Transwell migration and invasion assays. A xenograft tumor model in nude mice was established to assess the in vivo effects of Circ₀007552 on LUAD by measuring tumor size, weight, and growth rate. Bioinformatics analysis and dual-luciferase reporter gene assays were conducted to validate the interactions among Circ₀007552, miR-7974, and BAP1. Western blot was performed to detect the protein expression of BAP1.ResultsCirc₀007552 exhibited low expression in LUAD tissues and cells, correlating with clinicopathological features such as tumor size, lymph node metastasis, clinical stage, and poor prognosis. Both in vitro and in vivo experiments demonstrated that Circ₀007552 overexpression suppressed malignant biological behaviors of LUAD cells, whereas its knockdown exerted opposite effects. Mechanistically, Circ₀007552 functioned as a competing endogenous RNA (ceRNA) for miR-7974, negatively regulating its expression. Overexpression of miR-7974 partially reversed the tumor-suppressive effects of Circ₀007552 on LUAD cells. Furthermore, BAP1 was identified as a downstream target of miR-7974, and Circ₀007552 positively modulated BAP1 expression.ConclusionCirc₀007552 inhibits the development, progression, and metastasis of lung cancer by sponging miR-7974 to upregulate BAP1 expression. The present study further elucidates the underlying molecular mechanisms driving lung cancer progression.

BackgroundLung adenocarcinoma (LUAD), the most prevalent histological subtype of lung cancer, is a leading cause of global cancer mortality. Its pronounced heterogeneity poses a critical challenge, creating an urgent need for reliable biomarkers to accurately predict patient prognosis. Here, we focus on two critical tumor-promoting factors: lactylation and disulfidptosis.MethodsDifferential expression analysis, correlation analysis, and univariate survival analysis were performed using gene expression profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts to screen differentially expressed genes (DEGs), lactylation and disulfidptosis related genes (LDRGs), and prognosis-related genes (PGs). A prognostic model was constructed via LASSO regression, with its efficacy evaluated using calibration plots and decision curve analysis (DCA).The regulatory role of mitochondrial ribosomal protein large subunit 3 (MRPL3) in lung adenocarcinoma (LUAD) progression was validated through both in vivo and in vitro experiments.ResultsThis model demonstrated reliable predictive performance across the testing set, validation set, and external validation cohorts. MRPL3 was found to be overexpressed in LUAD tissues and correlated with poor prognosis, advanced tumor stage, and an immunosuppressive tumor microenvironment. In vitro, MRPL3 knockdown inhibited LUAD cell proliferation and migration, reduced intracellular lactylation levels, and downregulated glycolysis-related proteins. Under glucose deprivation, MRPL3-knockdown cells exhibited a more stable F-actin cytoskeleton, suggesting evasion of disulfidptosis via XCT suppression. In vivo, MRPL3 knockdown significantly suppressed xenograft tumor growth.ConclusionCollectively, this study establishes a robust prognostic model for LUAD and clarifies MRPL3’s role in regulating glycolytic-lactate metabolism and disulfidptosis to influence tumor progression and immune microenvironment remodeling. These findings provide a novel potential target and theoretical basis for LUAD prognosis assessment and targeted therapy.

Lung adenocarcinoma, the major form of lung cancer, is the deadliest cancer worldwide, due to its late diagnosis and its high heterogeneity. Indeed, lung adenocarcinoma exhibits pronounced inter- and intra-tumor heterogeneity cofounding precision medicine. Tumor heterogeneity is a clinical challenge driving tumor progression and drug resistance. Several key pieces of evidence demonstrated that lung adenocarcinoma results from the transformation of progenitor cells that accumulate genetic abnormalities. Thus, a better understanding of the cell of origin of lung adenocarcinoma represents an opportunity to unveil new therapeutic alternatives and stratify patient tumors. While the lung is remarkably quiescent during homeostasis, it presents an extensive ability to respond to injury and regenerate lost or damaged cells. As the lung is constantly exposed to potential insult, its regenerative potential is assured by several stem and progenitor cells. These can be induced to proliferate in response to injury as well as differentiate into multiple cell types. A better understanding of how genetic alterations and perturbed microenvironments impact progenitor-mediated tumorigenesis and treatment response is of the utmost importance to develop new therapeutic opportunities.

Lots of studies have shown that cyclin disorders can promote tumor development. This study aims to investigate the biological function and molecular mechanism of CCNB2 in lung adenocarcinoma (LUAD). LUAD data were downloaded from GEO database and TCGA-LUAD database. Differential analysis was conducted to find the differentially expressed miRNAs and mRNAs, while targeted prediction was done for the access of potential target mRNAs. Gene expression level was detected by qRT-PCR and Western blot in human LUAD cell lines A-427, A549, Calu-3, PC-9 and human bronchial epithelial cell line BEAS-2B. MTT, colony formation, Transwell and flow cytometry assays were used to detect cell proliferation, metastasis, and cell cycle changes of PC-9 cell line. The dual-luciferase reporter gene was used to detect the targeted binding relationship of the target miRNA and mRNA. CCNB2 was highly expressed and served as a biomarker indicating poor prognosis in LUAD patients. Cell function experiments confirmed the inhibitory effects of silencing CCNB2 on the proliferation, migration and invasion of LUAD cells and cell cycle was blocked in the G0/G1 phase. In addition, with regard to the regulatory mechanism, we demonstrated that miR-335-5p had binding sites with 3'-UTR of CCNB2, indicating that miR-335-5p could target the regulation expression of CCNB2. In subsequent cell function tests, overexpression of miR-335-5p inhibited the proliferation and metastasis of cancer cells, and the rescue experiments also verified that miR-335-5p could reverse the promotion of CCNB2 overexpression on the progress of cancer cells. In summary, our results revealed that miR-335-5p could target the down-regulation of CCNB2 to inhibit the occurrence and development of LUAD.

Circ₀009624 expression was increased in LUAD tissues and cells, and decreased in SAL‐treated LUAD cells. Furthermore, applying SAL might constrain malignant phenotypes and immune escape of LUAD cells partially through the circ₀009624‐mediated PD‐L1 pathway.

Due to the high heterogeneity of lung adenocarcinoma (LUAD), molecular subtype based on gene expression profiles is of great significance for diagnosis and prognosis prediction in patients with LUAD. Invasion‐related genes were obtained from the CancerSEA database, and LUAD expression profiles were downloaded from The Cancer Genome Atlas. The ConsensusClusterPlus was used to obtain molecular subtypes based on invasion‐related genes. The limma software package was used to identify differentially expressed genes (DEGs). A multi‐gene risk model was constructed by Lasso‐Cox analysis. A nomogram was also constructed based on risk scores and meaningful clinical features. 3 subtypes (C1, C2 and C3) based on the expression of 97 invasion‐related genes were obtained. C3 had the worst prognosis. A total of 669 DEGs were identified among the subtypes. Pathway enrichment analysis results showed that the DEGs were mainly enriched in the cell cycle, DNA replication, the p53 signalling pathway and other tumour‐related pathways. A 5‐gene signature (KRT6A, MELTF, IRX5, MS4A1 and CRTAC1) was identified by using Lasso‐Cox analysis. The training, validation and external independent cohorts proved that the model was robust and had better prediction ability than other lung cancer models. The gene expression results showed that the expression levels of MS4A1 and KRT6A in tumour tissues were higher than in normal tissues, while CRTAC1 expression in tumour tissues was lower than in normal tissues. The 5‐gene signature prognostic stratification system based on invasion‐related genes could be used to assess prognostic risk in patients with LUAD.

Lung cancer has emerged as a significant public health challenge and remains the leading cause of cancer-related mortality worldwide. Among various types of lung malignancies, lung adenocarcinoma (LUAD) stands as the most prevalent form. MicroRNAs (miRNAs) play a crucial role in gene regulation, and their involvement in cancer has been extensively explored. While several reviews have been published on miRNAs and lung cancer, there remains a gap in the review regarding miRNAs specifically in LUAD. In this review, we not only highlight the potential diagnostic, prognostic, and therapeutic implications of miRNAs in LUAD, but also present an inclusive overview of the extensive research conducted on miRNAs in this particular context.

BackgroundIntroduction: Circular RNAs (circRNAs) have been identified as significant contributors to the development and advancement of cancer. The objective of this study was to examine the expression and clinical implications of circRNA circ_(B)BS9 in lung adenocarcinoma (LUAD), as well as its potential modes of action.MethodsThe expression of Circ_(B)BS9 was examined in tissues and cell lines of LUAD through the utilization of microarray profiling, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot analysis. In this study, we assessed the impact of circ_(B)BS9 on the proliferation of LUAD cells, as well as its influence on ferroptosis and tumor formation. To analyze these effects, we employed CCK-8 assays and ferroptosis assays. The identification of proteins that interact with Circ_(B)BS9 was achieved through the utilization of RNA pull-down and mass spectrometry techniques. A putative regulatory network comprising circ_(B)BS9, miR-7150, and IFIT3 was established using bioinformatics study. The investigation also encompassed the examination of the correlation between the expression of IFIT3 and the invasion of immune cells.ResultsCirc_(B)BS9 was significantly downregulated in LUAD tissues and cell lines. Low circ_(B)BS9 expression correlated with poor prognosis. Functional experiments showed that circ_(B)BS9 overexpression inhibited LUAD cell proliferation and promoted ferroptosis in vitro and suppressed tumor growth in vivo. Mechanistically, circ_(B)BS9 was found to directly interact with IFIT3 and regulate its expression by acting as a sponge for miR-7150. Additionally, IFIT3 expression correlated positively with immune infiltration in LUAD.ConclusionCirc_(B)BS9 has been identified as a tumor suppressor in lung adenocarcinoma (LUAD) and holds promise as a diagnostic biomarker. The potential mechanism of action involves the modulation of ferroptosis and the immunological microenvironment through direct interaction with IFIT3 and competitive binding to miR-7150. The aforementioned findings offer new perspectives on the pathophysiology of LUAD and highlight circ_(B)BS9 as a potentially valuable target for therapeutic interventions.

Lung adenocarcinoma (LUAD), the major subtype of lung cancer, is among the leading cause of cancer-related death worldwide. Energy-related metabolic reprogramming metabolism is a hallmark of cancer shared by numerous cancer types, including LUAD. Nevertheless, the functional pathways and molecular mechanism by which FAM83A-AS1 acts in metabolic reprogramming in lung adenocarcinoma have not been fully elucidated. We used transwell, wound-healing scratch assay, and metabolic assays to explore the effect of FAM83A-AS1 in LUAD cell lines. Western blotting, Co-IP assays, and ubiquitination assays were used to detect the effects of FAM83A-AS1 on HIF-1α expression, degradation, and its binding to VHL. Moreover, an subcutaneous tumor formation assay was used to detect the effect of FAM83A-AS1 on LUAD. Herein, we identified FAM83A-AS1 as a metabolism-related lncRNA, which was highly correlated with glycolysis, hypoxia, and OXPHOS pathways in LUAD patients using bioinformatics analysis. In addition, we uncovered that FAM83A-AS1 could promote the migration and invasion of LUAD cells, as well as influence the stemness of LUAD cells and vitro. Moreover, FAM83A-AS1 was shown to promote glycolysis in LUAD cell lines and , and was found to influence the expression of genes related to glucose metabolism. Besides, we revealed that FAM83A-AS1 could affect glycolysis by regulating HIF-1α degradation. Finally, we found that FAM83A-AS1 knockdown could inhibit tumor growth and suppress the expression of HIF-1α and glycolysis-related genes . Our study demonstrates that FAM83A-AS1 contributes to LUAD proliferation and stemness via the HIF-1α/glycolysis axis, making it a potential biomarker and therapeutic target in LUAD patients.