Resistance to osimertinib in lung adenocarcinoma presents a significant hurdle in contemporary lung cancer therapy, with splicing dysregulation being instrumental in tumorigenesis and progression. The mechanism via which alternate splicing facilitates osimertinib resistance in lung cancer is still ambiguous. We aimed to examine the pivotal function of the splicing factor hnRNPA1 in osimertinib resistance in lung cancer. The impact of hnRNPA1 on osimertinib resistance in lung cancer was confirmed by small interfering RNA and CDX models. RNA-seq, RIP, CLIP-qPCR, and COIP methodologies were utilized to examine the mechanistic role of hnRNPA1 in osimertinib resistance in lung cancer. Furthermore, virtual docking was employed to evaluate natural small-molecule drugs that target hnRNPA1.Elevated levels of the splicing factor hnRNPA1 were detected in lung adenocarcinoma cells exhibiting resistance to osimertinib, and the silencing of hnRNPA1 enhanced the sensitivity of these resistant cells to osimertinib. Mechanistically, hnRNPA1 governs multiple splicing events linked to cancer, notably the splicing of NEDD4L. Decreased hnRNPA1 enhances the generation of short NEDD4L splice variants, resulting in the ubiquitination and degradation of EGFR, which sensitizes resistant cells to osimertinib. Moreover, hnRNPA1 undergoes methylation modification by PRMT7, which facilitates splicing activities. The research elucidated the mechanism responsible for aberrant splicing in osimertinib resistance in lung cancer and identified hnRNPA1 as a prospective therapeutic target for counteracting this resistance.

Objective This study investigates the prognostic value of the time interval (ΔT)measured from first-line therapy start to the sustained elevation of serum carcinoembryonic antigen (CEA) for progression-free survival (PFS) and overall survival (OS) in lung adenocarcinoma patients,and analyzes its correlation with other clinical-pathologic characteristics. Methods This retrospective study enrolled 225 pathologically confirmed, first-line treatment-naïve lung adenocarcinoma patients with complete clinical and follow-up data.Defining ΔT as the time interval from first-line therapy start to the first documented sustained CEA elevation (two consecutive measurements with ≥ 20% increase).Patients were dichotomized based on △T median value = 242 days and the optimal cut-off value for therapeutic efficacy determined by ROC curve analysis (134days).Baseline characteristics, objective response rate (ORR),and disease control rate (DCR) were compared between groups.Median PFS (mPFS) and OS were estimated using the Kaplan–Meier method and compared by log-rank test.Univariate and multivariate survival analyses were performed using Cox proportional-hazards models. Results Regardless of grouping by △T median value(242days) or △T cut-off value(134days),the “late CEA elevation” group exhibited significantly superior ORR,DCR,mPFS,and OS compared with the “early CEA elevation” group (all P < 0.001).Multivariate analysis identified sex,liver metastasis,and grouping by either median ΔT or cut-off ΔT as independent influencing factors for both mPFS and OS.Survival curves further confirmed marked prolongation of mPFS and OS in the “late elevation”versus“early elevation” cohorts. Conclusion The time interval from first-line therapy start to sustained CEA elevation remains a key predictor of therapeutic efficacy and prognosis in lung adenocarcinoma; a longer ΔT is correlated with better treatment response and more favorable survival outcomes.

BackgroundCSNK1D is a member of the CK1 family and is characterized by high conservation and widespread expression. It plays a regulatory role in the maintenance of numerous cellular processes and is expressed at low levels in normal tissues but is overexpressed in several types of cancer. All tumor tissues were pathologically diagnosed as lung adenocarcinoma.MethodsImmunohistochemistry (IHC) was used to retrospectively assess CSNK1D expression levels in 90 lung adenocarcinoma surgical tumor tissue microarrays (TMAs). All tumor tissues were pathologically diagnosed as lung adenocarcinoma. An enzyme-linked immunosorbent assay (ELISA) was employed to detect CSNK1D expression in serum samples from 22 lung adenocarcinoma patients. All tumor tissues were pathologically diagnosed as lung adenocarcinomaResultsCSNK1D was expressed in both the cytoplasm and nucleus, with higher levels in tumor tissues than in adjacent nontumor tissues. The results of survival analysis revealed that high CSNK1D expression was significantly associated with a favorable prognosis. The results of multivariate analysis, adjusted for clinicopathological features, indicated that high CSNK1D expression was an independent predictor of cancer-specific survival.

Plasticizers are widely used industrial chemicals, in addition, their extensive application has raised growing concerns about potential exposure-related health risks. Diisopentyl phthalate (DiPP), commonly used in the production of plastics and coatings, remains poorly characterized with respect to its toxicological effects. In this study, Caenorhabditis elegans was employed as the research model to evaluate the impact of early long-time exposure to DiPP on aging and innate immunity. The results demonstrated that DiPP exposure significantly shortened lifespan and induced the accumulation of lipofuscin and a reduced pharyngeal pumping rate, suggesting an accelerated aging phenotype. Molecular analysis revealed that DiPP upregulated the expression of daf-2 and age-1, while downregulating daf-16 and key components of the p38 MAPK signaling pathway. Additionally, DiPP exposure reduced nematode survival following Pseudomonas aeruginosa PA14 infection, indicating a decline in innate immunity. RT-qPCR and mutant validation experiments confirmed that both the insulin-like and p38 MAPK signaling pathways are implicated in DiPP-induced phenotypes consistent with accelerated immunological aging (defined here as an age-related decline in innate immune defenses, as measured by reduced pathogen resistance and decreased antimicrobial peptide gene expression). Collectively, these findings provide novel insights into the toxicological profile of DiPP and highlight its potential role in accelerating aging and impairing innate immunity.

Long noncoding RNAs (lncRNAs) are increasingly recognized as key regulators of lung adenocarcinoma (LUAD), yet for many lncRNAs the upstream repressors and downstream effector pathways remain unclear. Here, we identify MIR22HG as a frequently downregulated lncRNA in LUAD, and show that its low expression is associated with aggressive tumor behavior and poor clinical outcome. Functionally, MIR22HG restrains LUAD progression, as evidenced by reduced proliferation, migration, invasion, and xenograft growth upon MIR22HG restoration. Mechanistically, MIR22HG promotes Beclin1-associated autophagy and ferroptosis, providing a functional basis for its tumor-suppressive activity. We further demonstrate that SIN3A serves as an RNA-binding protein that negatively regulates MIR22HG at the post-transcriptional level. SIN3A depletion increases MIR22HG abundance, enhances autophagy- and ferroptosis-related signaling, and suppresses malignant phenotypes in LUAD cells. Importantly, genetic rescue experiments indicate that these SIN3A-dependent effects are partially mediated through MIR22HG, supporting a functional SIN3A-MIR22HG regulatory relationship. Collectively, our data delineate an SIN3A-MIR22HG-Beclin1 regulatory axis that links RNA-level repression to autophagy and ferroptosis control in LUAD and suggest that disruption of this pathway contributes to tumor progression. Targeting SIN3A-mediated repression of MIR22HG may, therefore, represent a potential therapeutic avenue for LUAD.

Objective: This study investigates the prognostic value of the time interval (ΔT)measured from first-line therapy start to the sustained elevation of serum carcinoembryonic antigen (CEA) for progression-free survival (PFS) and overall survival (OS) in lung adenocarcinoma patients,and analyzes its correlation with other clinical-pathologic characteristics. Methods: This retrospective study enrolled 225 pathologically confirmed, first-line treatment-naïve lung adenocarcinoma patients with complete clinical and follow-up data.Defining ΔT as the time interval from first-line therapy start to the first documented sustained CEA elevation (two consecutive measurements with ≥20% increase).Patients were dichotomized based on △T median value=242 days and the optimal cut-off value for therapeutic efficacy determined by ROC curve analysis (134days).Baseline characteristics, objective response rate (ORR),and disease control rate (DCR) were compared between groups.Median PFS (mPFS) and OS were estimated using the Kaplan–Meier method and compared by log-rank test.Univariate and multivariate survival analyses were performed using Cox proportional-hazards models. Results: Regardless of grouping by △T median value(242days) or △T cut-off value(134days）,the “late CEA elevation” group exhibited significantly superior ORR,DCR,mPFS,and OS compared with the “early CEA elevation” group (all P<0.001).Multivariate analysis identified sex,liver metastasis,and grouping by either median ΔT or cut-off ΔT as independent influencing factors for both mPFS and OS.Survival curves further confirmed marked prolongation of mPFS and OS in the “late elevation”versus“early elevation” cohorts. Conclusion: The time interval from first-line therapy start to sustained CEA elevation remains a key predictor of therapeutic efficacy and prognosis in lung adenocarcinoma; a longer ΔT is correlated with better treatment response and more favorable survival outcomes.

Malignant pleural effusion (MPE) and malignant ascites (MA) are common complications in advanced-stage cancers, often signifying disease progression and resistance to treatment. Compared to tissue biopsies or surgical specimens, materials derived from effusions offer advantages such as minimal invasiveness, ease of accessibility, and the feasibility of repeated collection during therapeutic interventions. Organoids generated from tumor cells in effusions, termed fluid-derived organoids (FDOs), have demonstrated the ability to maintain genetic heterogeneity and accurately replicate patient-specific tumor phenotypes. These characteristics position FDOs as promising models for investigating drug resistance mechanisms and informing personalized oncology strategies. In the context of lung cancer, organoids derived from pleural effusions have been employed to study acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and immunotherapy. Similarly, in ovarian and gastrointestinal cancers, organoids derived from ascites have proven to be valuable platforms for examining chemotherapy resistance and conducting drug sensitivity testing. FDOs have shown significant potential for translational applications by effectively correlating ex vivo drug responses with clinical outcomes, thus facilitating real-time monitoring of resistance evolution. However, several challenges remain, such as achieving culture standardization, maintaining the integrity of tumor microenvironment components, and integrating with multi-omics approaches. This review provides a comprehensive overview of recent advancements in the use of pleural effusion- and ascites-derived organoids for drug resistance research, underscores their applications in personalized oncology, and explores future research directions.

Acquired resistance to osimertinib poses a major challenge in treating EGFR-mutant lung adenocarcinoma (LUAD). Here, we demonstrate that shikonin, a natural compound from Lithospermum erythrorhizon, synergizes with osimertinib to overcome this resistance by inducing ferroptosis. In osimertinib-resistant LUAD cells (PC9-OR/H1975-OR), the shikonin-osimertinib combination significantly enhances cytotoxicity and suppresses proliferation while triggering ferroptotic events, including reactive oxygen species accumulation, lipid peroxidation, and iron overload alongside glutathione depletion. RNA-sequencing identifies Hes family BHLH transcription factor 1 (HES1) downregulation as crucial to this process. HES1 knockdown replicates the combination's effects, confirming its key role. Mechanistically, ATF3 is identified as a direct transcriptional target of HES1, with HES1 binding to the ATF3 promoter (-786 to -779 nt) to repress its transcription. The shikonin-osimertinib combination relieves this repression, leading to ATF3-mediated suppression of the ferroptosis regulators SLC7A11 and GPX4. In vivo, this combination potently inhibits tumor growth in xenograft models without observable toxicity. Our study reveals a novel HES1/ATF3 axis governing ferroptosis and proposes shikonin as a promising therapeutic adjuvant to overcome osimertinib resistance in LUAD.

OBJECTIVE:As global smoking rates decline, Lung Cancer in Never-Smokers (LCINS) has emerged as a distinct and increasingly important clinical entity. However, its underlying pathogenesis remains poorly understood, highlighting the need to identify circulating molecular determinants and candidate biomarkers. METHODS:Genetic instruments for plasma proteins were obtained from pQTL datasets (Fenland study and UK Biobank Pharma Proteomics Project), while summary statistics for LCINS were sourced from TRICL-ILCCO. Two-sample Mendelian Randomization (MR) was performed using inverse-variance weighting as the primary approach, complemented by sensitivity analyses for heterogeneity (Cochran's Q), horizontal pleiotropy (MR-Egger intercept), and outlier detection (MR-PRESSO). Tissue-level validation was conducted using CPTAC proteomic data. Further analyses, including Bayesian colocalization, Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO) enrichment, and mediation analysis, were applied to investigate shared genetic architecture, functional pathways, and immune-mediated mechanisms. RESULTS:Among 543 cis-acting plasma proteins evaluated in the discovery phase, 35 exhibited evidence of association with LCINS risk, including 15 positively and 20 inversely associated proteins. After False Discovery Rate (FDR) correction, only genetically proxied plasma RARRES1 remained statistically significant (OR = 1.17, adjusted P = 2.72 × 10-5), and this finding was replicated in an independent cohort. Bayesian colocalization supported a shared causal variant (PPH4 = 0.83). Functional enrichment analyses implicated RARRES1-related networks in immune regulation and extracellular processes. Two-step MR mediation analysis nominated CD16-CD56 intensity on NKT cells as a potential immune-mediated pathway, accounting for an estimated 11.8% of the genetic effect. DISCUSSION:This study prioritizes genetically proxied plasma RARRES1 as a candidate protein associated with LCINS risk and highlights CD16-CD56 intensity on NKT cells as a potential immune-related mechanism. These findings provide biologically plausible evidence supporting a role for RARRES1 in LCINS pathogenesis and its potential utility in biomarker development. CONCLUSION:Genetically proxied plasma RARRES1 is associated with increased LCINS risk and may contribute to disease susceptibility through immune-related alterations involving NKT-cell phenotypes. RARRES1 represents a promising candidate for future mechanistic studies and blood-based diagnostic biomarker development in LCINS.

ABSTRACT Purpose In non‐small cell lung cancer (NSCLC) patients resistant to first‐ or second‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), only half develop the T790M mutation and thus qualify for the treatment using third‐generation EGFR‐TKIs. For T790M‐negative patients, chemotherapy is the recommended second‐line treatment. We compared the efficacy between third‐generation EGFR‐TKIs and chemotherapy with or without first/second‐generation EGFR‐TKIs in T790M‐negative patients. Patients This study included T790M‐negative patients with EGFR‐mutated advanced NSCLC and progressing after first‐line treatment with first‐ or second‐generation EGFR‐TKIs. Data on clinical characteristics, disease features, and survival were collected, including general conditions, medical history, imaging, histology, and molecular profiling. Results Of 82 patients progressing after first‐ or second‐generation EGFR‐TKIs without acquiring T790M, 45 received third‐generation EGFR‐TKIs and 37 received chemotherapy and/or first/second‐generation EGFR‐TKIs. We found that third‐generation EGFR‐TKIs led to significantly longer median progression‐free survival (mPFS) than other treatments [10.20 months vs. 5.70 months, p = 0.017]. Subgroup analyses indicated that third‐generation EGFR‐TKIs had similar mPFS to the chemotherapy group but were significantly superior to first/second‐generation EGFR‐TKIs with or without chemotherapy (10.20 months vs. 4.80 months, p < 0.001; 10.20 months vs. 3.30 months, p = 0.004). The median overall survival (mOS) for patients treated with third‐generation EGFR‐TKIs and with non‐third‐generation therapy was 39.80 months (95% CI 23.14 to 56.46) and 32.40 months (95% CI 18.71 to 46.09), p = 0.408, respectively. Conclusions Third‐generation EGFR‐TKIs significantly improved mPFS in T790M‐negative patients with EGFR‐mutated advanced NSCLC and resistant to first‐line treatment with first‐ or second‐generation EGFR‐TKIs. Trial Registration ChiCTR2500096109

Long non-coding RNAs (lncRNAs) are involved in tumorigenesis. The telomerase RNA component (TERC) is a lncRNA that functions as an essential template for the addition of the telomere repeats; its dysfunctions has been associated with various human diseases. However, how dysregulation of TERC expression and activity affects lung adenocarcinoma (LUAD) progression remains elusive. RNA sequencing (RNA-seq) analysis was used to compare the expression levels of TERC in cancerous and adjacent normal lung tissues. Functional assays of TERC in LUAD cell lines were performed by siRNA-mediated knockdown. Cell proliferation was assessed using the water-soluble tetrazolium salt-1 (WST-1) assay, while colony formation capability was evaluated through colony formation assays. Cell migration and invasion were analyzed using Transwell assays. Reactive oxygen species (ROS) levels were determined by flow cytometry and examined by fluorescence microscopy. The morphology of mitochondria was observed using transmission electron microscopy. Protein expression was analyzed by western blot. The formation of autophagosomes was monitored by fluorescence microscopy following the expression of fluorescently tagged LC3. Xenograft experiments were conducted to test the inhibition of TERC knockdown in LUAD proliferation in vivo. RNA-seq analysis showed that the expression of TERC was upregulated in lung cancer tissues. Silencing TERC suppressed the proliferation, migration, and invasion of lung cancer cells in vitro. Additionally, it inhibited the growth of pulmonary xenografts in mice in vivo. Mechanistic analyses indicated that silencing of TERC increased the expression of autophagy-related proteins LC3B, Beclin-1, and AMP-activated protein kinase (AMPK), while the expression of p62 protein and ferroptosis-regulated proteins GPX4 and SLC7A11 were diminished. Importantly, inhibition of AMPK function counterbalanced the effects of TERC knockdown on autophagy and ferroptosis in LUAD cells. These findings reveal that suppression of TERC in lung cancer promotes autophagy and ferroptosis via regulation of AMPK. They help to understand the mechanism underlying TERC activity in tumorigenesis. It will be of interest to determine the clinical significance of TERC dysregulation in lung cancer.

Background:The MIR205 host gene (MIR205HG) has been reported to play important roles in various cancers. However, its role in the occurrence and development of lung cancer remains to be clarified. This study aimed to analyze the function and molecular mechanisms of MIR205HG in lung adenocarcinoma (LUAD). Methods:The RNA sequencing (RNA-Seq) dataset was used to examine MIR205HG expression. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze the expression of MIR205HG in LUAD tissues and adjacent tissues. It was also employed to examine the expression of MIR205HG in LUAD cell lines. Water-Soluble Tetrazolium 1 (WST-1), colony formation assay, transwell assay and flow cytometry assay were used to explore the function of MIR205HG in lung cancer cells. Immunofluorescence assay was applied to examine the formation of autophagosomes. Western blot assay was used to analyze the expression of autophagy-related proteins and ferroptosis-related protein. Results:MIR205HG was highly expressed in LUAD tissues compared to adjacent tissues. Knockdown of MIR205HG expression prevented cell growth, migration, and invasion, and promoted apoptosis in LUAD cells. Western blot results showed that autophagy-related proteins, AMPK, BECLIN-1, and LC3B, were increased, while p62, mTOR and the ferroptosis-related protein GPX4 were decreased after MIR205HG knockdown. Conclusions:Knockdown of MIR205HG inhibits the development of LUAD through autophagy and ferroptosis pathways, suggesting that MIR205HG may be a potential target in the diagnosis and therapeutic treatment of LUAD.

Background:Lung cancer, especially non-small cell lung cancer (NSCLC), is a leading cause of cancer mortality. Epidermal growth factor receptor (EGFR) mutations drive NSCLC progression but also sensitize tumors to EGFR-tyrosine kinase inhibitors (TKIs). However, the response rate to targeted therapy is only 70%, and most patients experience disease progression 9 to 14 months after first- or second-generation EGFR-TKI treatment. This study aims to examine the association between super-amplification refractory mutation system (ARMS)-derived ΔCt values [mutant DNA cycle threshold (Ct) value relative to the endogenous reference gene (Ct) value] and EGFR mutation (EGFRm) abundance in predicting the efficacy and prognosis of EGFR-TKIs in NSCLC patients. Methods:The present retrospective research encompassed 139 patients with stage IIIB-IV NSCLC treated with EGFR-TKIs. Patients were categorized based on super-ARMS ΔCt values and Kaplan-Meier, and Cox regression models were used to evaluate the outcomes in survival and independent influencing factors, thus establishing the optimal ΔCt value for EGFR-TKIs response. Results:High mutation abundance, defined by ΔCt ≤3.76, was correlated with increased objective response rate (ORR) (61.2% vs. 36.8%, P=0.003) and longer median progression-free survival (mPFS) (20.9 vs. 15.8 months, log-rank P=0.005) compared to low abundance. The optimal ΔCt cut-off predictive of EGFR-TKIs response was 4.335. Patients with ΔCt ≤4.335 demonstrated superior ORR (64.6% vs. 28.1%, P<0.001) and mPFS (20.9 vs. 13.5 months, log-rank P<0.001) compared to those with ΔCt >4.335. Multivariate Cox analysis identified median ΔCt value group (ΔCt ≤3.76 or ΔCt >3.76), the optimal ΔCt cut-off value group (ΔCt ≤4.335 or ΔCt >4.335), brain metastasis, liver metastasis, EGFRm status, performance status (PS) score, and the generation of EGFR-TKIs as independent predictors of PFS in first-line EGFR-TKIs-treated patients. Conclusions:Stratification based on ΔCt values derived from the super-ARMS system can predict the efficacy and clinical prognosis of first-line EGFR-TKI treatment in NSCLC patients. Additionally, higher mutation abundance may contribute to the superior efficacy and prognosis of EGFR-TKIs in patients with exon 19 deletions compared to those with the 21L858R mutation.

ObjectiveThis study conducts a bibliometric analysis of artificial intelligence (AI) applications in cervical cancer to provide a comprehensive overview of the research landscape and current advancements.MethodsRelevant publications on cervical cancer and AI were retrieved from the Web of Science Core Collection. Bibliometric analysis was performed using CiteSpace and VOSviewer to assess publication trends, authorship, country and institutional contributions, journal sources, and keyword co-occurrence patterns.ResultsFrom 1996 to 2024, our analysis of 770 publications on cervical cancer and AI showed a surge in research, with 86% published in the last 5 years. China (315 pubs, 32%) and the US (155 pubs, 16%) were the top contributors. Key institutions were the Chinese Academy of Sciences, Southern Medical University, and Huazhong University of Science and Technology. Research hotspots included disease prediction, image analysis, and machine learning in cervical cancer. Schiffman led in publications (12) and citations (207). China had the highest citations (3,819). Top journals were “Diagnostics,” “Scientific Reports,” and “Frontiers in Oncology.” Keywords like “machine learning” and “deep learning” indicated current research trends. This study maps the field's growth, highlighting key contributors and topics.ConclusionThis bibliometric analysis provides valuable insights into research trends and hotspots, guiding future studies and fostering collaboration to enhance AI applications in cervical cancer.

This study aims to systematically evaluate the global distribution, academic impact, and technological trends of ultrasound technology in lung cancer research from 2000 to 2024 through bibliometric analysis, providing references for future research directions. Based on the Web of Science Core Collection database, 2,617 publications from 2000 to 2024 were included. Bibliometric analysis was conducted using VOSviewer and CiteSpace, covering publication trends, countries, institutions, authors, journals, highly cited literature, and keyword co-occurrence networks. Metrics such as publication volume, citation count, and total link strength (TLS) were quantitatively assessed. From 2000 to 2024, the annual number of publications on ultrasound in lung cancer diagnosis and treatment surged from 19 to 218, with the last five years accounting for 38

Aspartate/asparagine-β-hydroxylase (ASPH), a type II transmembrane α-ketoglutarate-dependent hydroxylase, is frequently overexpressed in various cancers. However, its role in lung adenocarcinoma (LUAD) remains unclear. Here, we analyzed ASPH expression in LUAD and normal lung tissues using bioinformatic tools, and evaluated its association with clinicopathological characteristics and patient prognosis. High ASPH expression correlated with advanced disease and poor survival, and served as an independent prognostic factor. Functional assays, including Transwell, scratch healing, and murine lung metastasis models, demonstrated that ASPH promotes LUAD cell migration and metastasis. The potential molecular mechanisms by which ASPH exerts its function in LUAD were explored by transcriptome sequencing analysis and immunoprecipitation combined with mass spectrometry (IP-MS). Further analysis showed that ASPH enhances activation of the MAPK and Notch signaling pathways through RUVBL2 interaction. Collectively, our findings suggest that ASPH contributes to LUAD progression by engaging RUVBL2 and activating key oncogenic signaling cascades, highlighting its potential as a prognostic biomarker and therapeutic target.

Lung cancer remains a leading cause of cancer-related mortality worldwide. Its progression is intricately associated with the dynamic regulation of autophagy and RNA-binding proteins (RBPs), which play crucial roles in mRNA stability, alternative splicing, and cellular stress responses. This review aims to systematically analyze the mechanisms through which RBPs and autophagy contribute to lung cancer progression and explore potential therapeutic strategies targeting these pathways. Methods: We reviewed recent studies on the molecular mechanisms by which RBPs regulate tumor proliferation, metabolic adaptation, and their interaction with autophagy. The review also examines the dual roles of autophagy in lung cancer, highlighting its context-dependent effects on cell survival and death. The interactions and regulatory networks between RBPs and autophagy involve multiple levels of regulation. RBPs can directly influence autophagy processes and act as microRNA (miRNA) sponges to regulate mRNA stability. The modulation of RBPs affects the expression of autophagy-related genes (ATGs) and autophagosome formation. Additionally, RBPs participate in complex regulatory interactions with non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and other proteins. This review proposes innovative therapeutic strategies that combine RBP-targeting approaches (e.g., small molecule inhibitors, CRISPR gene editing) with autophagy modulators (e.g., mTOR inhibitors, chloroquine) to enhance treatment efficacy. Nanoparticle drug delivery systems and epigenetic regulation offer further opportunities for targeted interventions. This review lays a theoretical foundation for advancing lung cancer research and provides novel insights into synergistic therapies that target both RBPs and autophagy to improve treatment outcomes for lung cancer.

Background:The standard of care for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) is induction chemotherapy (ICT) followed by concurrent chemoradiation (CCRT). However, the ideal ICT regimen for LA-NPC remains unclear. We conducted a meta-analysis to evaluate the survival outcomes, responses, and incidences of toxicities between taxane, cisplatin and fluorouracil (TPF) and cisplatin and fluorouracil (PF) ICT regimens plus CCRT in LA-NPC.Methods:A systematic review and meta-analysis of the literature was conducted to compare the efficacy and safety of TPF versus PF followed by CCRT with cisplatin every 3 weeks or weekly cisplatin and intensity-modulated radiotherapy in LA-NPC.Results:Three studies with 2482 patients met the inclusion criteria. ICT with the TPF regimen plus CCRT resulted in a significantly improved progression-free survival (hazard ratios [HR] 0.84 [95% CI 0.73-0.96], P = .01), overall survival (HR 0.83 [95% CI 0.71-0.97], P = .02), and 3-year locoregional recurrence-free survival (risk ratios [RR] 1.03 [95% CI 1.01-1.06], P = .009) compared with the PF regimen plus CCRT in LA-NPC. However, distant metastasis-free survival was not statistically significant (P = .07). The incidence of grade 3 or 4 neutropenia (RR 2.08 [95% CI 1.84-2.36]) and diarrhea (RR 1.94 [95% CI 1.07-3.52]) during ICT was higher in the TPF group than in the PF group.Conclusions:In terms of progression-free survival, overall survival, locoregional recurrence-free survival, in the era of intensity-modulated radiotherapy, the TPF plus CCRT with cisplatin is superior to PF plus CCRT with cisplatin in LA-NPC. Thus, the TPF plus CCRT regimen appears to be a reasonable treatment option, and further confirmation by prospective studies is needed.

[This corrects the article DOI: 10.32604/or.2023.030771.].

Lung adenocarcinoma (LUAD) is the most common malignant tumor in the lung. Circular RNAs (circRNAs) play critical roles in cancer progression. However, the functions and mechanisms of circPLEKHH2 in regulating cancer progression and autophagy in LUAD are largely unknown. Our research team identified circPLEKHH2 (annotated as hsa_circ_0120106) which is significantly down-regulated in LUAD via RNA-seq in 14 pairs of LUAD tissues. The expression level of circPLEKHH2 in patient tissue has potential diagnostic value to distinguish LUAD tissue from normal lung tissue. Functionally, circPLEKHH2 promoted autophagy and inhibited LUAD cell proliferation, invasion, migration, and tumor growth. Mechanistically, we identified that circPLEKHH2 promoted autophagy via the AKT/mTOR signaling pathway, and the mTOR inhibitor rapamycin can reverse the oncogenic effects of circPLEKHH2 silencing. IGF2BP3 can bind to circPLEKHH2 to inhibit its expression. These results revealed that as a tumor suppressor, IGF2BP3-regulated circPLEKHH2 promotes autophagy through the AKT/mTOR signaling pathway to inhibit the occurrence and progression of LUAD. Therefore, circPLEKHH2 could be a potential therapeutic target for LUAD.