Plaque-Hepatic Targeting Nanotherapy Disrupts the PCSK9-LOX-1 Axis to Suppress oxLDL in Atherosclerosis.

Non-small cell lung cancer (NSCLC) accounts for roughly 85% of the total incidence of lung cancer []. Despite considerable advances in therapeutic strategies, which include targeted therapies and immunotherapies, the general prognosis of patients diagnosed with NSCLC is still not good due to late diagnosis, high metastatic rates, and acquired drug resistance [, ]. As a result, there is an urgent, critical need in NSCLC research to identify novel, reliable molecular biomarkers for early detection, accurate prognosis prediction, and development of new therapeutic targets. Currently, 18 F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18 F-FDG PET/CT) is a recommended clinical tool for lymph node metastasis (LNM) detection, and its derived metabolic parameters such as maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) have been confirmed to be effective in predicting preoperative LNM in resectable NSCLC []. Many natural compounds exert anti-tumor effects by targeting classic oncogenic signaling pathways in NSCLC. For instance, allicin, a natural active component from garlic, has been proven to inhibit NSCLC cell proliferation and migration by targeting the EGFR/PI3K/AKT pathway, a core oncogenic pathway in NSCLC []. In addition to natural product intervention, exploring novel molecular regulatory axes is another important direction for NSCLC targeted therapy. Long non-coding RNA (lncRNAs) exert their functions through intricate mechanisms such as chromatin remodeling, transcriptional regulation, post-transcriptional processing, and sponging microRNAs (miRNAs), thereby influencing fundamental cancer hallmarks like cell proliferation, apoptosis, invasion, and metastasis []. Numerous lncRNAs, such as HOTAIR [], MALAT1 [], and XIST [], have been extensively documented as key drivers or suppressors in NSCLC pathogenesis. The lncRNA LY86-AS1 has recently emerged as a potential player in human diseases. Indeed, LY86-AS1 proved discriminative for diagnosing between plasma cell leukemia and multiple myeloma []. Besides, downregulation of LY86-AS1 has been associated with T2DM due to its potential role as a diagnostic marker []. Tao Yi et al. through bioinformatics analysis of LUAD datasets, found that LY86-AS1 is downregulated in lung adenocarcinoma (LUAD), the most common pathological subtype of NSCLC, and predicted that this downregulation may affect the clinical outcomes of LUAD patients []. In line with this, Sheng Yu et al. identified LY86-AS1 as a cuproptosis-related lncRNA and proposed it as a potential prognostic factor for LUAD patients via bioinformatic screening []. While these bioinformatic studies provided preliminary clues for the role of LY86-AS1 in lung cancer, this study further verifies and expands these findings by using clinical NSCLC tissue samples and in vitro cell experiments, and the expression pattern and regulatory mechanisms of LY86-AS1 have not been well established in the entire NSCLC population encompassing all pathological subtypes. The oncogenic potential of miR-132 is manifested through its promotion of cell proliferation, migration, and invasion []. Exosomal miR-132-3p from lung cancer activates normal human lung fibroblasts, contributing to the pathogenesis of interstitial lung disease []. Overexpression of miR-132-3p was indeed found in NSCLC [, ]. On another front, RB1CC1 plays a tumor-suppressive role in prostate cancer [] and is frequently mutated in breast cancer, acting as a prototypical tumor suppressor []. In lung cancer, the nuclear localization of RB1CC1 is linked to lipid peroxidation, and its associated signaling enhances tumor cell sensitivity to ferroptosis, implying that RB1CC1-targeted therapies may be advantageous []. Despite these individual findings, the relationship between LY86-AS1, miR-132-3p, and RB1CC1 and their regulatory function within NSCLC requires further investigation.