Nanomaterial-based drug delivery systems are susceptible to premature drug leakage and systemic toxicity due to lack of specific targeting, and live-cell drug delivery is also prone to be restricted by drug carrier–cell interactions. Here, a method is established to adsorb drug-loaded nanomaterials externally to the live cells, which reduces cytotoxicity caused by drug uptake and improves the bioactivity of the carrier cells and drug release at the lesion site. It was found that polyphenols act like “double-sided tape” to bridge metal–organic framework (MOF) nanoparticles with live macrophages (Mφ), attaching MOFs to the Mφ surface and minimizing intracellular uptake, with no negative effect on cell proliferation. On this basis, a “macrophage missile” with peroxymonosulfate (PMS)-loaded MOF nanoparticles on the cell surface was constructed. As a “propellant”, the Mφ, in which bioactivity is preserved, can selectively identify and target tumor cells, precisely bringing nanomedicines to the lesion. MOF nanoparticles are used to load and catalyze PMS, which acts as an exogenous source of reactive oxygen species, showing higher efficacy and lower toxicity in an oxygen-independent manner. The primary study results demonstrate that this innovative combination of biology and nanomaterials remarkably enhances tumor targeting and therapeutic efficacy while reducing systemic side effects. This approach is expected to provide a more effective and safer treatment for lung cancer and holds promise for broader applications in other cancer therapies.

Background/Aims: Serum apolipoprotein A1 (apoA1) has been reported to be abnormally expressed in several malignancies. However, the prognostic role of apoA1 in solid tumors is still controversial. We conducted this meta-analysis to obtain a more accurate evaluation of prognostic significance of apoA1 in Chinese patients with solid tumors. Methods: A comprehensive literature search of electronic databases was carried out up to August 2018. We included studies investigating the association between pretreatment serum apoA1 level and clinicopathological features, including survival outcomes, in solid tumors. Hazard ratios (HRs) and odds ratio (ORs) with 95% confidence intervals (CIs) were applied as effect size estimates. Results: A total of 13 studies and 8052 patients were included in our meta-analysis. Elevated level of pretreatment serum apoA1 was markedly associated with an improved OS (pooled HR = 0.608, 95% CI = 0.557 – 0.665, P < 0.001). The statistical significances were observed in all cancer types, including digestive system malignancies (pooled HR = 0.633; 95% CI = 0.550–0.727; P < 0.001), urinary system cancers (pooled HR = 0.471; 95% CI = 0.352–0.630; P < 0.001), nasopharyngeal cancer (pooled HR = 0.642; 95% CI = 0.538–0.766; P < 0.001) and non-small cell lung cancer (pooled HR = 0.526; 95% CI = 0.329–0.841; P = 0.007), but not in breast cancer (pooled HR = 0.573; 95% CI = 0.266–1.246; P = 0.155). Meanwhile, cancer patients with a low level of serum apoA1 suffered an unfavorable DFS (pooled HR = 0.714, 95% CI = 0.603 – 0.845, P < 0.001). Moreover, abnormal serum apoA1 was significantly correlated to tumor size (pooled OR = 0.640, 95% CI = 0.475 – 0.863, P = 0.003), tumor differentiation (pooled HR = 0.724, 95% CI = 0.565 – 0.929, P = 0.011), and tumor stage (pooled HR = 0.493, 95% CI = 0.384 – 0.633, P < 0.001). Conclusion: Elevated level of pretreatment serum apoA1 was significantly associated with longer survival in patients with solid tumors. Pretreatment serum apoA1 could serve as a novel positive factor for malignant patient prognosis in Chinese population.

Background 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. Objectives 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. Results 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. Conclusions 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. Graphical Abstract

Long non-coding RNAs play critical roles in the development of lung cancer by functioning as tumor suppressors or oncogenes. Changes in the expression of LINC01279 have been associated with cell differentiation and human diseases. However, the mechanism underlying LINC01279 activity in tumorigenesis is not clear. Here, we analyzed the function of LINC01279 in lung adenocarcinoma using clinical samples, xenografts, and non-small-cell lung cancer cell lines. We found that LINC01279 is highly expressed in lung adenocarcinoma and may be considered as a predictive factor for this cancer. Knockdown of LINC01279 prevents tumor growth in xenografts and in cancer cell lines by activating autophagy and apoptosis. Molecularly, we revealed that LINC01279 regulates the expression of focal adhesion kinase and extracellular-regulated kinase signaling. In addition, it complexes with and stabilizes the transcriptional co-repressor SIN3A protein. Suppression of focal adhesion kinase and SIN3A also induces apoptosis and prevents tumor progression, suggesting that they may at least in part mediate the oncogenic activity of LINC01279. These results identify LINC01279 as a possible oncogene that plays an important role in the development of lung cancer. Our findings provide insights into the mechanism underlying LINC01279-mediated oncogenesis of lung adenocarcinoma. They may help to discover potential therapeutic targets for cancer diagnosis and prognosis.

Lung adenocarcinoma (LUAD) is one of the deadliest cancers. Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-targeted therapy is an important approach for treating LUAD. However, the development of acquired resistance poses a serious clinical challenge. Our objective was to explore the differentially expressed genes (DEGs) associated with EGFR and detect biomarkers for diagnosing and treating osimertinib resistance in LUAD patients. LUAD datasets were downloaded from public databases. Differential expression analysis was performed to screen DEGs, and prognostic modules were constructed by Cox regression. Enrichment analysis, gene regulatory network analysis and immune microenvironment analysis were employed to explore the underlying mechanisms in LUAD. Finally, the expression of prognosis module genes (PMGs) was validated in 8 LUAD tissue specimens and 5 cell lines by qRT-PCR. In total, 13 differential module genes (BIRC3, CCT6A, CPLX2, GLCCI1, GSTA1, HLA-DQB2, ID1, KCTD12, MUC15, NOTUM, NT5E, TCIM, and TM4SF4) were screened for the construction of a prognostic module. Notably, CCT6A and KCTD12 demonstrated excellent accuracy in the diagnosis of LUAD. Immune dysregulation and BIRC3, HLA-DQB2, KCTD12, and NT5E expression were significantly associated with invasive immune cells in LUAD patients. The expression level of CCT6A was highest in PC9-OR and H1975-OR cells, while the expression level of KCTD12 was highest in paracancerous tissue and HBE cells. The constructed prognostic model showed promise in predicting the survival of LUAD patients. Notably, KCTD12 and CCT6A might be candidate biomarkers for improving diagnostic performance and guiding individualized therapy for EGFR-TKI-resistant LUAD patients.

PFKP (Phosphofructokinase, Platelet Type isoform), as an essential metabolic enzyme, contributes to the high glycolysis rates seen in cancers while its role in oncogenic pathways, especially from a non-metabolic aspect, is not fully understood. We found that PFKP was highly expressed in NSCLC and was related to poor patient survival. Knockdown of PFKP significantly inhibited cell proliferation, colony formation, invasion, and migration of NSCLC cells. Nanoparticles-mediated PFKP silencing can inhibit tumor growth in vivo. Mechanistically, we found that PFKP can bind with AXL and promote its phosphorylation at Y779, thus activating the AXL signaling pathway and promoting MET phosphorylation. In addition, several glycolysis, glutaminolysis, and TCA cycle proteins were downregulated following PFKP silencing. PFKP has an oncogenic role in cancer progression in vitro and in vivo. Beyond its known role in glycolysis, PFKP also has a non-metabolic function in affecting lung cancer progression by interacting with the AXL-MET axis, thus indicating a potential therapeutic target for lung cancer.