Background: Sorting nexin 9 (SNX9) is involved in intracellular vesicle transport and signal transduction, and its abnormal expression is related to the occurrence and development of a variety of cancers. In lung adenocarcinoma (LUAD), the role and molecular mechanism of SNX9 remain unclear. This study combined bioinformatics analysis and in vitro validation to explore its expression characteristics in LUAD, its specific effects on tumor development, and its potential molecular mechanism and prognostic value. Methods: In this study, the expression data and clinical information of SNX9 in LUAD were obtained from Tumor Immune Estimation Resource (TIMER) 2.0, The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases, and the relationship between SNX9 expression and prognosis was analyzed using TCGA database patient information and Kaplan-Meier plotter, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to reveal the mechanism of SNX9. Gene set enrichment analysis (GSEA) enrichment analysis highlighted the pathways and biological processes rich in gene sets in SNX9 high-expression samples, thereby providing insights into associated enrichment pathways. The effects of SNX9 on the proliferation, migration and invasion of LUAD cells were detected by Western blot and in vitro experiments. Results: The results of this study showed that the expression level of SNX9 in LUAD tissues was significantly higher than that in normal lung epithelial cells, and its high expression was closely related to the increase in tumor grade and poor prognosis of patients. Functional enrichment analysis showed that SNX9-related genes were concentrated in epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) and cell adhesion processes in LUAD, suggesting that the increased expression of SNX9 is positively correlated with the enhanced invasion ability of LUAD cells. In vitro experiments also showed that knockdown of endogenous SNX9 significantly inhibited the proliferation, migration and invasion of A549 and H1299 cells. Conclusions: This study shows that SNX9 is overexpressed in LUAD and is associated with poor prognosis. We speculate that SNX9 is expected to be a prognostic marker and a potential therapeutic target for LUAD, providing a new direction and theoretical basis for related research and clinical application.

Background: Limonin is one of the major active ingredients of citrus. In the present study, the anti-angiogenic and anti-metastatic effects of limonin were investigated. Methods: The Molecular docking assay was carried out to assess the binding ability of limonin with VEGFR2 receptor. MTS assay was used to detect the effect of limonin on the proliferation of breast cancer cells (MDA-MB-231, MCF-7). The Wound-healing and Transwell chamber invasion assays were used to detect the inhibition effect of limonin on migration and invasion of HUVECs cells or breast cancer cells. The capillary-like tube formation assay and Matrixgel plug experiment were used to further measure the in vivo anti-angiogenic activity of limonin. Western blot, RNA isolation, microarray data analysis and RT-PCR were used to explore the molecular mechanism of limonin in suppressing breast cancer angiogenesis and metastasis. Left ventricular tumor metastasis model and caudal vein tumor metastasis model of breast cancer were both applied to verify in vivo anti-metastatic effects. Results: Limonin dose-dependently inhibited the vascular endothelial growth factor (VEGF)-mediated tyrosine phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) by blocking VEGF binding to VEGFR2 and suppressing constitutive STAT3 activation in human umbilical vein endothelial cells. Limonin effectively inhibited VEGF-induced endothelial cell proliferation, migration and tubular-structure formation in vitro and markedly reduced VEGF-triggered neovascularization in mouse matrigel plugs in vivo. Moreover, limonin treatment led to a remarkable suppression of tumor metastasis by decreasing the phosphorylation of insulin growth factor receptor 1-mediated STAT3 and the expression levels of its downstream members MMP-9 and VEGF in breast cancer cells. The data further showed that limonin increased the levels of the negative STAT3 regulator SHP-1 in breast cancer cells. Conclusions: Limonin is a promising anti-angiogenic and anti-metastatic candidate compound that can be further optimized as a therapeutic agent for breast cancer.

Treatment of human estrogen receptor (ER)‑positive breast cancer (ER+ BC) using conventional chemotherapy remains a challenge and is often ineffective as a result of tumor metastasis. The present study aimed to investigate the ability of narasin, an ionophore antibiotic, to potentially inhibit tumor metastasis and growth in human ER+ BC. Narasin was found to have significant inhibitory abilities on cell proliferation, migration and invasion in ER+ BC cell lines MCF‑7 and T47D compared with the triple‑negative BC cell MDA‑MB‑231. For the in vivo studies, narasin effectively decreased the number of tumor metastasis nodules, tumor volume and weight without apparent toxicity in human MCF‑7 nude mouse left ventricle injection tumor metastasis and xenograft models. Mechanistically, it demonstrated that exposure to TGF‑β or IL‑6 induced the expression of epithelial‑mesenchymal transition (EMT) markers in ER+ BC cell lines. On the contrary, narasin dose‑dependently reversed EMT by increasing the expression of E‑cadherin and decreasing the expression of N‑cadherin, vimentin, β‑catenin and zinc finger E‑box‑binding homeobox 1 at the protein and gene expression levels. Gene microarray, molecular docking and western blotting were performed to demonstrate that those protein and gene expression levels are regulated by the inactivation of the TGF‑β/phosphorylated (p)‑SMAD3 and IL‑6/p‑STAT3 signaling pathways. Taken together, these findings indicated that narasin may be a promising candidate that can be further optimized for the treatment of human ER+ BC.

Colorectal cancer (CRC) is a major global health problem with high morbidity and mortality rates. Surgical resection is the main treatment for early-stage CRC, but detecting it early is challenging. Therefore, effective therapeutic targets for advanced patients are still lacking. Exosomes, tiny vesicles in body fluids, play a crucial role in tumor metastasis, immune regulation, and drug resistance. Interestingly, they can even serve as a biomarker for cancer diagnosis and prognosis. Studies have shown that exosomes can carry miRNA, mediate the polarization of M1/M2 macrophages, promote the proliferation and metastasis of cancer cells, and affect the prognosis of CRC. Since the gastrointestinal tract has many macrophages, understanding the mechanism behind exosomal miRNA-mediated macrophage polarization in CRC treatment is crucial. This article summarizes recent advancements in the study of exosomal miRNAs in CRC and their potential as diagnostic and prognostic markers.

Objective: This study aimed to investigate the safety and efficacy of the computed tomography (CT)-guided hook-wire localization technique in thoracoscopic surgery for small pulmonary nodules (≤ 10 mm) and to identify the risk factors for localization-related complications. Methods: The medical records of 150 patients with small pulmonary nodules treated from January 2018 to June 2021 were retrospectively analyzed. According to preoperative hook-wire positioning status, they were divided into the localization group (50 cases) or the control group (100 cases). The operation time, intraoperative blood loss, hospital stay, and conversion rate to thoracotomy were recorded and compared between groups. Uni- and multivariate binary logistic regression analysis was used to identify the risk factors for localization-related complications. Results: A total of 58 nodules were localized in 50 patients in the localization group, and the localization success rate was 98.3% (57/58). In one case, the positioning pin fell off before wedge resection was performed. The mean nodule diameter was 7.05 mm (range, 2.8–10.0 mm), while the mean depth from the pleura was 22.40 mm (range, 5.47–79.47 mm). There were 8 cases (16%) of asymptomatic pneumothorax, 2 (4%) of intrapulmonary hemorrhage, and 1 (2%) of pleural reaction.The mean operation time of the localization group (103.88 ± 41.74 min) was significantly shorter than that of the control group (133.30 ± 45.42 min) (P < 0.05). The mean intraoperative blood loss of the localization group (44.20 ± 34.17 mL) was significantly lower than that of the control group (112.30 ± 219.90 mL) (P < 0.05). The mean hospital stay of the localization group (7.96 ± 2.34 days) was significantly shorter than that of the control group (9.21 ± 3.25 days).Multivariate binary logistic analysis showed that localization times of small pulmonary nodules in the localization group was an independent risk factor for localization-related pneumothorax. Conclusions: Our results suggest that the CT-guided hook-wire localization technique is beneficial for localizing small pulmonary nodules. Specifically, it is helpful for the diagnosis and treatment of early lung cancer because it can accurately remove lesions, decrease intraoperative blood loss, shorten operation time and hospitalization stay, and reduce thoracotomy conversion rate. Simultaneous positioning of multiple nodules can easily lead to positioning-related pneumothorax.