In pursuit of meeting the ever-rising demand for cancer therapies, cross-presentation-based glyconanovaccines (GNVs) targeting C-type lectin receptors (CLRs) on DCs have shown significant potential as cutting-edge cancer immunotherapy. GNVs are an attractive approach to induce anti-cancer cytotoxic T lymphocyte responses. Despite immune checkpoints (ICs) being well established and an obstacle to the success of GNVs, glycan-lectin circuits are emerging as unique checkpoints due to their immunomodulatory functions. Given the role of aberrant tumor glycosylation in promoting immune evasion, mitigating these effects is crucial for the efficacy of GNVs. Lectins, such as siglecs and galectins, are detrimental to the tumor immune landscape as they promote an immunosuppressive TME. From this perspective, this review aims to explore glycan-lectin ICs and their influence on the efficacy of GNVs. We aim to discuss various ICs in the TME followed by drawbacks of immune checkpoint inhibitors (ICIs). We will also emphasize the altered glycosylation profile of tumors, addressing their immunosuppressive nature along with ways in which CLRs, siglecs, and galectins contribute to immune evasion and cancer progression. Considering the resistance towards ICIs, current and prospective approaches for targeting glycan-lectin circuits and future prospects of these endeavors in harnessing the full potential of GNVs will also be highlighted.

Cisplatin (DDP) resistance significantly affects the survival rate of patients with ovarian cancer (OC). Autophagy is recognized as a common cause of resistance to DDP. This study aimed to investigate the impact of salidroside on OC progression and explore its potential regulatory effects on DDP resistance and autophagy. A DDP-resistant A2780 (A2780/DDP) cell line was induced by exposure to increasing DDP concentrations. The protein levels of autophagy proteins (p62, Beclin-1, ATG5, and LC3 II/LC3 I), apoptosis proteins (cleaved caspase-3 and cleaved caspase-9), and PI3K/AKT/mTOR pathway were determined by western blotting. Autophagic vacuoles in cells were observed with LC3 dyeing with confocal fluorescent microscopy. Cell viability and apoptosis were evaluated by cell counting kit-8 assays and flow cytometry. RT-qPCR was conducted to measure the relative levels of various lncRNAs in A2780 or A2780/DDP cells. A xenograft model was established by subcutaneous injection of 1 × 107 A2780 cells into the posterior flank of nude mice. Tumor size and weight were recorded. The expression of Ki67, cleaved caspase-3 and LC3 in tumor tissues was assessed by immunohistochemistry staining. The biodistribution of DDP in organs and blood of normal nude mice and tumors of tumor-bearing mice was detected using the ICP-MS. Hematoxylin-eosin staining was used to assess the histopathological changes of kidney, liver, and spleen sections. For in vitro analysis, autophagy was enhanced in DDP-resistant A2780 cells. Additionally, salidroside inhibits DDP resistance to A2780 cells via autophagy inhibition. Mechanistically, salidroside downregulated CRNDE in DDP-resistant A2780 cells. CRNDE knockdown inhibited autophagy, while CRNDE overexpression reversed the protective effects of salidroside. Additionally, salidroside activated the PI3K/AKT/mTOR pathway in DDP-resistant A2780 cells, and inhibition of PI3K reversed the effect of salidroside on inhibiting autophagy and apoptosis of A2780/DDP cells. For in vivo analysis, salidroside inhibited tumor growth, autophagy, and nephrotoxicity of DDP. Additionally, salidroside downregulated CRNDE and activated PI3K/AKT/mTOR signaling in vivo. Salidroside prevents autophagy-mediated DDP resistance in OC by downregulating lncRNA CRNDE and activating the PI3K/AKT/mTOR pathway.

Gastric cancer remains a leading cause of cancer mortality, with oxaliplatin (L-OHP) resistance posing a major therapeutic challenge. Ginsenosides have shown potential in addressing chemoresistance.

This study aimed to investigate whether ginsenoside Compound K (CK), a derivative of protopanaxadiol ginsenosides, could overcome L-OHP resistance in gastric cancer cells.

The anti-cancer effects of CK were investigated using L-OHP-resistant HGC27/L cells through comprehensive in vitro experiments. Cell viability, migration, invasion, apoptosis, and colony formation were evaluated under CK treatment alone or combined with L-OHP. Drug efflux was specifically assessed using Rhodamine 123 staining. To understand the molecular mechanism, network pharmacology and molecular docking analyses were employed, which identified the PI3K/Akt pathway as a crucial target of CK. This finding was further validated through Western blotting and RT-qPCR analyses, focusing on PI3K/Akt signaling components and EMT markers. Finally, drug-resistant gastric cancer xenograft models were established to evaluate the therapeutic efficacy of CK alone and in combination with L-OHP in vivo.

CK effectively suppressed cell viability, migration, invasion, drug efflux, and colony formation while enhancing apoptosis in resistant cells. Mechanistically, CK inhibited the PI3K/Akt pathway, leading to reduced P-glycoprotein (P-gp) expression and EMT reversal. These effects were confirmed using PI3K pathway modulators. In xenograft models, CK significantly inhibited tumor growth and reduced PI3K/Akt activity, P-gp expression, and EMT markers.

This study demonstrates that CK overcomes L-OHP resistance through PI3K/Akt pathway inhibition and EMT prevention, suggesting that combining CK with L-OHP may improve outcomes in chemoresistant gastric cancer patients.

Small cell lung cancer (SCLC) is one of the malignancies with the worst prognosis, and there have been no major breakthroughs in its treatment for a long time. The majority of patients are diagnosed at the extensive stage, where the only option is chemotherapy, and even the addition of immune checkpoint inhibitors results in only modest benefits. The characterization of the molecular mechanisms behind therapy resistance has relevance in finding novel therapeutic approaches. Previous studies showed the possibility of annexin A1's (ANXA1) involvement in the immunosuppressive tumor microenvironment in SCLC, and there are studies showing the direct effects of ANXA1 modulation on cancer cell aggressiveness.

We aimed to characterize the roles of ANXA1 expression using publicly available transcriptomic data, the RNA-seq-based predictive algorithms EPIC and ESTIMATE, and immunohistochemistry on patient samples. For the in vitro studies, we silenced ANXA1 expression with short hairpin RNA in three SCLC cell lines, measured the growth rate with the trypan blue exclusion assay, assessed the chemosensitivity to cisplatin and etoposide with the Presto BlueTM viability assay, and performed Western blots to assess changes in the levels of metabolic and mesenchymal markers and transcriptional drivers.

ANXA1-high tumors are associated with significantly increased immune infiltrates, stromality, and tumor-associated macrophages (TAMs). The ANXA1 protein is expressed on tumor cells and TAMs at the tissue level. ANXA1 silencing in H841 cells did not affect the growth rate; in SW1271 cells, shANXA1 cells grew significantly slower than shCTRL cells. Meanwhile, in H1048 cells, proliferation was significantly faster. Despite the different growth rates of the tested cell lines, ANXA1 silencing decreased the chemosensitivity to both cisplatin and etoposide in all three cell lines. Gene expression changes in mesenchymal markers, metabolic markers, dominant transcriptional drivers, and immune-relevant molecules were also characterized.

This is the first comprehensive characterization of ANXA1 in SCLC to reveal its role in the tumor's cell biology and the TME, aiming to boost further research in the field.

The stability of membrane contact sites is critically dependent on Endoplasmic Reticulum mitochondria contact tethering complexes (EMCTCs), and dysregulation of these sites has been implicated in neuropathic diseases. In this study, we examined the role of Annexin A10 (Anxa10), a calcium-dependent protein, in neuropathic pain by investigating its influence on EMCTCs dysregulation. Using RNA sequencing, western blotting, and behavioral assays, we observed that spared nerve injury (SNI)-induced neuropathic pain significantly increased Anxa10 expression levels within the spinal dorsal horn (SDH) of mice. By employing cell-specific gene regulation via the Cre/loxp system, we utilized loxp-modified adeno-associated virus vectors to modulate Anxa10 expression in GAD2-Cre (inhibitory neurons), vGlut2-Cre (excitatory neurons), and Fos-Cre (activity-induced neurons) transgenic mice. Our results demonstrated that specific down-regulation of Anxa10 in excitatory neurons within the SDH alleviated neuropathic pain, whereas up-regulation of Anxa10, regardless of cell type, induced spontaneous pain in mice. Ultrastructural analysis of the endoplasmic reticulum (ER) and mitochondria, as well as double immunofluorescence staining, revealed that downregulation of Anxa10 mitigated the SNI-induced reduction in ER-mitochondrial distance. Additionally, it attenuated the SNI-induced upregulation of key components of EMCTCs, including IP3R, GRP75, and VDAC1, while preventing the SNI-induced downregulation of NCX3 expression. Furthermore, we formulated and validated the hypothesis that SGK1 and PI3K are positioned downstream of Anxa10. The up-regulation of Anxa10 compromised mitochondrial integrity and disrupted mitochondrial networks, ultimately leading to elevated oxidative stress. Collectively, these findings suggest that Anxa10 represents a promising therapeutic target for correcting EMCTCs dysregulation and mitigating neuropathic pain.

Squamous cell carcinoma of the tongue, a common and aggressive malignancy, poses a substantial threat to health and well-being. Despite the promising results of combination therapy with dihydroartemisinin (DHA) and oxaliplatin (Oxa) in various cancers, its effectiveness in treating tongue squamous cell carcinoma had not been explored prior to this study. Our research found that DHA significantly enhances the sensitivity of tongue squamous cell carcinoma cells to Oxa, even at very low concentrations. The combination treatment was observed to modulate the activity of CDK1 and Cyclin B1, arresting the cell cycle in the G2 phase. Additionally, it reduces mitochondrial membrane potential, prompting the release of cytochrome c and activating cleaved caspase-3, which promotes apoptosis. Notably, surface plasmon resonance and immunoprecipitation experiments revealed that DHA targets and attenuates CDK1 modification, weakening its interaction with STAT3 protein. This leads to reduced expression of anti-apoptotic genes and facilitates programmed cell death in CAL-27 cells. The findings underscore the potential of DHA and Oxa as a potent therapeutic strategy for tongue squamous cell carcinoma, opening avenues for clinical application and further exploration into its mechanistic pathways.

Chemotherapy resistance is a major challenge in the treatment of intermediate and advanced gastric cancer (GC). This study aimed to recognize oxaliplatin resistance-related genes (OXARGs) in GC and to explore their role and mechanism in oxaliplatin resistance of GC.

OXARGs with prognostic value in GC were analyzed using GC oxaliplatin resistance data from the GEO and TCGA databases. RT-qPCR and WB assay were applied to verify the expression of MT2A, NOTCH1 and SLC7A5 in oxaliplatin-resistant GC cells (HGC27R and MKN45R). The effect of SLC7A5 on the malignant phenotype of oxaliplatin-resistant GC cells was verified by CCK-8, EDU, TUNEL, colony formation, wound healing, transwell assay, tumor bearing experiments and WB assay.

Bioinformatics analysis and experimental validation indicate that SLC7A5 was a target for oxaliplatin-resistance in GC. Knockdown of SLC7A5 obviously decreased the viability, migration, and invasion of oxaliplatin-resistant GC cells in vitro and tumor growth in vivo. It also increased the apoptosis levels and BAX expression, and reduced the expression of BCL2, MMP 2 and MMP9. Additionally, the knockdown of SLC7A5 enhanced the sensitivity of oxaliplatin-resistant GC cells to oxaliplatin both in vitro and in vivo. Furthermore, knockdown of SLC7A5 downregulated the expression of HK2, LDHA, Glut1, and PDK1 both in vivo and in vitro, leading to increased extracellular glucose levels and decreased lactate levels. However, glutathione significantly attenuated the regulatory effect of SLC7A5 knockdown on the malignant phenotype of oxaliplatin-resistant GC cells.

Not Applicable.

Knockdown of SLC7A5 inhibits malignant progression and attenuates oxaliplatin resistance in GC by suppressing glycolysis.

Gastric cancer (GC) is a type of malignant tumor that seriously endangers human health. As the understanding of the mechanisms underlying gastric cancer deepens, in recent years, investigations on gastric cancer stem cells (GCSCs) have garnered significant interest. They are pivotal in the onset, progression, recurrence, and pharmacoresistance of GC. Comprehensive research on GCSCs is expected to provide new strategies for the diagnosis and treatment of GC. This article endeavors to comprehensively assess the current status and future trends of GCSCs research through bibliometric analysis, thereby providing a valuable reference for further in - depth studies in this field.

English - language academic journals related to GCSCs research in the Web of Science database were retrieved. Subsequently, VOSviewer was utilized to conduct network collinear analysis of the exported source institutions, literature authors, references, and keywords. And CiteSpace was used to perform statistical analysis of the annual publication count, keyword clustering, references, and keyword burst.

A total of 3882 documents that met the criteria were incorporated. The quantity of published papers has shown a consistent upward trend annually since 2003. Among the authors of the literature, multiple stable core author groups represented by Zhu, Wei, Wang, Mei, Xu, Wenrong, etc. have been formed. There are 335 associated institutions in total. The Japan National Cancer Center has the strongest relevance and the largest number of published papers. There are 7 clustering labels formed among the keywords, including main clustering modules such as activation, cancer stem cells, DNA content aneuploidy, and expression. 25 burst keywords were generated, and the burst keywords in the past two years include mesenchymal stem cells, drug resistance, proliferation, etc. The emergence of references indicates that eight references have been cited up to now and are the focus of current research.

The research overview of GCSCs in the past 30 years was visually presented by visual maps. In the past decade, scholars' research in this field has gradually intensified, and the development trend is good. Through the deeper study of the GCSCs mechanism, intervention GCSCs in the future will be a new promising treatment approach for GC patients. This hot topic still deserves more attention in the future.

Gastric cancer (GC) remains one of the most common types of cancer, ranking fifth among cancer-related deaths worldwide. Chemotherapy is an effective treatment for advanced GC. However, the development of chemotherapy resistance, which involves the malfunction of several signaling pathways and is the consequence of numerous variables interacting, seriously affects patient treatment and leads to poor clinical outcomes. Therefore, in order to treat GC, it is imperative to find novel medications that will increase chemotherapy sensitivity and reverse chemotherapy resistance. Traditional Chinese medicine (TCM) has been extensively researched as an adjuvant medication in recent years. It has been shown to have anticancer benefits and to be crucial in enhancing chemotherapy sensitivity and reducing chemotherapy resistance. Given this, the mechanism of treatment resistance in GC is summed up in this work. The theoretical foundation for TCM as a sensitizer in adjuvant treatment of GC is established by introducing the primary signal pathways and possible targets implicated in improving chemotherapy sensitivity and reversing chemotherapy resistance of GC by TCM and active ingredients.

Colorectal cancer (CRC) is a leading cause of cancer-related mortality globally. Although tumor immunotherapy is widely recognized for treating unresectable CRC, challenges such as ineffective immunotherapy and drug resistance remain prevalent. While intratumor microbiome-derived butyrate has been implicated in promoting lung cancer metastasis, its role in CRC chemoresistance is not well understood. This study aimed to explore the relationship between intratumor butyrate and chemoresistance in CRC.

We performed a comprehensive analysis of the microbiome composition in CRC patients with varying resistance-free survival (RFS) durations, utilizing 16S rRNA sequencing. Furthermore, we assessed the prognostic significance of circulating microbiome DNA (cmDNA) and examined the effects of exogenous butyrate supplementation on the chemosensitivity of CRC cell lines.

Our 16S sequencing analysis revealed a reduction in microbial diversity within tumor samples of patients with resistance, as indicated by metrics such as observed taxonomic units, Shannon, and Simpson indices. Notably, Roseburia and Fusobacteria emerged as prominent biomarkers for the resistance group, whereas Bifidobacterium, Helicobacter, and Akkermansia were identified as biomarkers for the non-resistant group. Utilizing a Lasso regression model, we identified six genera-Roseburia, Helicobacter, Gardnerella, Flavonifractor, Coprococcus, and Anaerostipes-that significantly correlated with recurrence-free survival. Furthermore, both the intratumor microbiome signature and circulating microbiome DNA were effective in accurately predicting CRC resistance. Experimental assays, including CCK8 and wound-healing, demonstrated that intratumor microbiome-derived butyrate enhances the proliferation and migration of HCT15 cells in a time- and concentration-dependent manner. Cell survival analysis further indicated that butyrate treatment significantly increased the IC50 value, suggesting heightened drug resistance in HCT15 cells. Mechanistically, this resistance was attributed to butyrate's activation of the PI3K-AKT signaling pathway.

Our results suggest that intratumor microbiome-derived butyrate contributes to chemoresistance in colorectal cancer, highlighting the potential prognostic and therapeutic significance of the intratumor microbiome.

The purpose of this study was to investigate the role of DGUOK in the progression of colorectal cancer (CRC) and its impact on the sensitivity of CRC cells to 5-FU treatment.

We conducted bioinformatics analysis and qRT-PCR to evaluate DGUOK expression in CRC tissues/cells. Cell viability of CRC cells treated with 5-FU was assessed using CCK-8 and colony formation assays. Autophagy levels were determined through immunofluorescence assays and Western blot analysis. Additionally, the influence of p-p38 on autophagy was investigated via Western blotting. A rescue assay was performed to confirm whether DGUOK/p38 affects 5-FU sensitivity in CRC cells through autophagy.

Our findings indicate that DGUOK is upregulated in CRC tissues compared to normal tissues, correlating with increased cell proliferation and migration. Functionally, inhibition of DGUOK enhances autophagy, thereby decreasing the sensitivity of CRC cells to 5-FU. This effect is partly mediated by DGUOK's impact on the mitogen-activated protein kinase (MAPK) pathway, specifically promoting the phosphorylation of p38 MAPK, a crucial regulator in autophagy pathways.

These results suggest that DGUOK could serve as a novel marker for predicting the efficacy of 5-FU in CRC treatment.

Pancreatic cancer remains one of the most lethal malignancies, with limited treatment options and poor prognosis. A common characteristic among pancreatic cancer patients is the biomechanically altered tumor microenvironment (TME), which among others is responsible for the elevated mechanical stresses in the tumor interior. Although significant research has elucidated the effect of mechanical stress on cancer cell proliferation and migration, it has not yet been investigated how it could affect cancer cell drug sensitivity. Here, we demonstrated that mechanical stress triggers autophagy activation, correlated with increased resistance to oxaliplatin treatment in pancreatic cancer cells. Our results demonstrate that inhibition of autophagy using hydroxychloroquine (HCQ) enhanced the oxaliplatin-induced apoptotic cell death in pancreatic cancer cells exposed to mechanical stress. The combined treatment of HCQ with losartan, a known modulator of mechanical abnormalities in tumors, synergistically enhanced the therapeutic efficacy of oxaliplatin in murine pancreatic tumor models. Furthermore, our study revealed that the use of HCQ enhanced the efficacy of losartan to alleviate mechanical stress levels and restore blood vessel integrity beyond its role in autophagy modulation. These findings underscore the potential of co-targeting mechanical stresses and autophagy as a promising therapeutic strategy to overcome drug resistance and increase chemotherapy efficacy.

Chemotherapy is a key treatment option for gastric cancer, but over 50% of patients develop either inherent or acquired resistance to these drugs, resulting in a 5-year survival rate of only about 20%. The primary treatment for advanced gastric cancer typically involves chemotherapy based on platinum or fluorouracil. Several factors can contribute to platinum resistance, including decreased drug uptake, increased drug efflux or metabolism, enhanced DNA repair, activation of pro-survival pathways, and inhibition of pro-apoptotic pathways. In recent years, there has been significant progress in biology aimed at finding innovative and more effective methods to overcome chemotherapy resistance. Small interfering RNAs (siRNAs) have emerged as a significant advancement in gene expression regulation, showing promise in enhancing the sensitivity of gastric cancer cells to chemotherapy drugs. However, siRNA therapies still face major challenges, particularly in terms of stability and efficient delivery in vivo. This article discusses the advances in siRNA therapy and its potential role in overcoming resistance to chemotherapeutic drugs such as cisplatin, 5-FU, doxorubicin, and paclitaxel in the treatment of gastric cancer.

The annexin superfamily protein, Annexin A1, initially recognized for its glucocorticoid-induced phospholipase A2-inhibitory activities, has emerged as a crucial player in diverse cellular processes, including cancer. This review explores the multifaceted roles of Anx-A1 in cancer chemoresistance, an area largely unexplored. Anx-A1's involvement in anti-inflammatory processes, its complex phosphorylation patterns, and its context-dependent switch from anti-to pro-inflammatory in cancer highlights its intricate regulatory mechanisms. Recent studies highlight Anx-A1's paradoxical roles in different cancers, exhibiting both up- and down-regulation in a tissue-specific manner, impacting different hallmark features of cancer. Mechanistically, Anx-A1 modulates drug efflux transporters, influences cancer stem cell populations, DNA damages and participates in epithelial-mesenchymal transition. This review aims to explore Anx-A1's role in chemoresistance-associated pathways across various cancers, elucidating its impact on survival signaling cascades including PI3K/AKT, MAPK/ERK, PKC/JNK/P-gp pathways and NFκ-B signalling. This review also reveals the clinical implications of Anx-A1 dysregulation in treatment response, its potential as a prognostic biomarker, and therapeutic targeting strategies, including the promising Anx-A1 N-terminal mimetic peptide Ac2-26. Understanding Anx-A1's intricate involvement in chemoresistance offers exciting prospects for refining cancer therapies and improving treatment outcomes.

Oxaliplatin is the most common chemotherapeutic agent for patients with colorectal cancer. However, its anti-cancer efficacy is restricted by drug resistance occurring through several mechanisms, including autophagy. Liensinine exerts a considerable anti-tumor effect and can regulate autophagy. Inhibition of autophagy is a strategy to reverse resistance to oxaliplatin. The aim of this study was to check if liensinine can enhance the therapeutic efficacy of oxaliplatin in colorectal cancer and if so, elucidate its mechanism.

Two colorectal cancer cell lines, HCT116 and LoVo, and one normal intestinal epithelial cell, NCM-460 were used for in vitro experiments. Cell Counting Kit-8 (CCK-8), colony formation, and flow cytometry assays were used to evaluate the cytotoxicity of liensinine and oxaliplatin. Network pharmacology analysis and Human XL Oncology Array were used to screen targets of liensinine. Transfections and autophagy regulators were used to confirm these targets. The relationship between the target and clinical effect of oxaliplatin was analyzed. Patient-derived xenograft (PDX) models were used to validate the effects of liensinine and oxaliplatin.

CCK-8 and colony formation assays both showed that the combination treatment of liensinine and oxaliplatin exerted synergistic effects. Results of the network pharmacology analysis and Human XL Oncology Array suggested that liensinine can inhibit autophagy by targeting HIF-1α/eNOS. HIF-1α was identified as the key factor modulated by liensinine in autophagy and induces resistance to oxaliplatin. HIF-1α levels in tumor cells and prognosis for FOLFOX were negatively correlated in clinical data. The results from three PDX models with different HIF-1α levels showed their association with intrinsic and acquired resistance to oxaliplatin in these models, which could be reversed by liensinine.

Research on the relationship between HIF-1α levels and the clinical effect of oxaliplatin is lacking, and whether liensinine regulates HIF-1α is unknown. Our findings suggest that liensinine overcomes the resistance of colorectal cancer cells to oxaliplatin by suppressing HIF-1α levels to inhibit autophagy. Our findings can contribute to improving prognosis following colorectal cancer therapy.

Gastric cancer (GC) has a high mortality rate worldwide. Despite significant progress in GC diagnosis and treatment, the prognosis for affected patients still remains unfavorable.

To identify important candidate genes related to the development of GC and identify potential pathogenic mechanisms through comprehensive bioinformatics analysis.

The Gene Expression Omnibus database was used to obtain the GSE183136 dataset, which includes a total of 135 GC samples. The limma package in R software was employed to identify differentially expressed genes (DEGs). Thereafter, enrichment analyses of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for the gene modules using the clusterProfile package in R software. The protein-protein interaction (PPI) networks of target genes were constructed using STRING and visualized by Cytoscape software. The common hub genes that emerged in the cohort of DEGs that was retrieved from the GEPIA database were then screened using a Venn Diagram. The expression levels of these overlapping genes in stomach adenocarcinoma samples and non-tumor samples and their association with prognosis in GC patients were also obtained from the GEPIA database and Kaplan-Meier curves. Moreover, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were performed to determine the mRNA and protein levels of glutamic-pyruvic transaminase (GPT) in GC and normal immortalized cell lines. In addition, cell viability, cell cycle distribution, migration and invasion were evaluated by cell counting kit-8, flow cytometry and transwell assays. Furthermore, we also conducted a retrospective analysis on 70 GC patients diagnosed and surgically treated in Wenzhou Central Hospital, Dingli Clinical College of Wenzhou Medical University, The Second Affiliated Hospital of Shanghai University between January 2017 to December 2020. The tumor and adjacent normal samples were collected from the patients to determine the potential association between the expression level of GPT and the clinical as well as pathological features of GC patients.

We selected 19214 genes from the GSE183136 dataset, among which there were 250 downregulated genes and 401 upregulated genes in the tumor samples of stage III-IV in comparison to those in tumor samples of stage I-II with a P-value < 0.05. In addition, GO and KEGG results revealed that the various upregulated DEGs were mainly enriched in plasma membrane and neuroactive ligand-receptor interaction, whereas the downregulated DEGs were primarily enriched in cytosol and pancreatic secretion, vascular smooth muscle contraction and biosynthesis of the different cofactors. Furthermore, PPI networks were constructed based on the various upregulated and downregulated genes, and there were a total 15 upregulated and 10 downregulated hub genes. After a comprehensive analysis, several hub genes, including runt-related transcription factor 2 (RUNX2), salmonella pathogenicity island 1 (SPI1), lysyl oxidase (LOX), fibrillin 1 (FBN1) and GPT, displayed prognostic values. Interestingly, it was observed that GPT was downregulated in GC cells and its upregulation could suppress the malignant phenotypes of GC cells. Furthermore, the expression level of GPT was found to be associated with age, lymph node metastasis, pathological staging and distant metastasis (P < 0.05).

RUNX2, SPI1, LOX, FBN1 and GPT were identified key hub genes in GC by bioinformatics analysis. GPT was significantly associated with the prognosis of GC, and its upregulation can effectively inhibit the proliferative, migrative and invasive capabilities of GC cells.

Cystatin SA (CST2) belongs to the superfamily of cysteine protease inhibitors. Emerging research indicates that CST2 is often dysregulated across various cancers. Its role and molecular mechanisms in gastric cancer remain underexplored. This study aims to explore the expression and function of CST2 in gastric cancer.

CST2 expression was analyzed and validated through Western blot. CST2 overexpression was induced by lentivirus in GC cells, and the correlation between CST2 expression levels and downstream signaling pathways was assessed. In addition, multiple assays, including cell proliferation, colony formation, wound-healing, and transwell migration/invasion, were considered to ascertain the influence of CST2 overexpression on gastric cancer. The cell cycle and apoptosis were detected by flow cytometry.

CST2 expression at the protein level was decreased to be reduced in both gastric cancer tissues and cell lines, and CST2 expression attenuate gastric cancer growth, an effect restricted to gastric cancer cells and absent in gastric epithelial GES-1 cells. Furthermore, CST2 was demonstrated to improve chemosensitivity to Oxaliplatin in gastric cancer cells through the PI3K/AKT signaling pathway.

These findings indicate that CST2 is downregulated at the protein level in gastric cancer tissues and cell lines. Additionally, CST2 was found to attenuate the growth of gastric cancer cells and to enhance sensitivity to Oxaliplatin through the PI3K/AKT signaling pathway, specific to gastric cancer cell lines. CST2 may serve as a tumor suppressor gene increasing sensitivity to Oxaliplatin in gastric cancer.

Gastric cancer (GC) is a malignant tumor that originates from the epithelium of the gastric mucosa. The latest global cancer statistics show that GC ranks fifth in incidence and fourth in mortality among all cancers, posing a serious threat to public health. While early-stage GC is primarily treated through surgery, chemotherapy is the frontline option for advanced cases. Currently, commonly used chemotherapy regimens include FOLFOX (oxaliplatin + leucovorin + 5-fluorouracil) and XELOX (oxaliplatin + capecitabine). However, with the widespread use of chemotherapy, an increasing number of cases of drug resistance have emerged. This article primarily explores the potential mechanisms of chemotherapy resistance in GC patients from five perspectives: cell death, tumor microenvironment, non-coding RNA, epigenetics, and epithelial-mesenchymal transition. Additionally, it proposes feasibility strategies to overcome drug resistance from four angles: cancer stem cells, tumor microenvironment, natural products, and combined therapy. The hope is that this article will provide guidance for researchers in the field and bring hope to more GC patients.

Autophagy is a cellular catabolic process characterized by the formation of double-membrane autophagosomes. Transmission electron microscopy is the most rigorous method to clearly visualize autophagic engulfment and degradation. A large number of studies have shown that autophagy is closely related to the digestion, secretion, and regeneration of gastrointestinal (GI) cells. However, the role of autophagy in GI diseases remains controversial. This article focuses on the morphological and biochemical characteristics of autophagy in GI diseases, in order to provide new ideas for their diagnosis and treatment.

In non-small cell lung cancer (NSCLC), metastasis is the most common phenotype, and autophagy plays a vital role in its regulation. However, there are limited data on how autophagy-related genes and metastasis-related genes affect NSCLC progression. Our goal was to identify the genes that regulate autophagy and metastasis in NSCLC, and to assess the underlying mechanisms in this current study. RNA sequencing data from public databases were used to screen differentially expressed autophagy- and metastasis-associated genes. Enrichment analyses and immune correlations were conducted to identify hub genes and potential regulating pathways in NSCLC. In this study, we found that CCL2 expression was highly expressed in NSCLC tissues and high CCL2 level was correlated with strong infiltration in lung tissues from NSCLC patients. Overexpression of CCL2 can enhance the metastasis of NSCLC cells in nude mice. Furthermore, CCL2 activated the PI3K/Akt/mTOR signalling pathway axis, promoted epithelial-mesenchymal transition (EMT), and blocked the autophagic flux in NSCLC cells. Therefore, our results indicate that CCL2 promotes metastasis and EMT of NSCLC via PI3K/Akt/mTOR axis and autophagy signalling pathways. We believe that CCL2 could be a probable target for the diagnosis and therapeutics of NSCLC, and this study may expand our understanding of lung cancer.

Annexins are cytosolic proteins with conserved three-dimensional structures that bind acidic phospholipids in cellular membranes at elevated Ca2+ levels. Through this they act as Ca2+-regulated membrane binding modules that organize membrane lipids, facilitating cellular membrane transport but also displaying extracellular activities. Recent discoveries highlight annexins as sensors and regulators of cellular and organismal stress, controlling inflammatory reactions in mammals, environmental stress in plants, and cellular responses to plasma membrane rupture. Here, we describe the role of annexins as Ca2+-regulated membrane binding modules that sense and respond to cellular stress and share our view on future research directions in the field.

Gastric cancer is a most malignancy in digestive tract worldwide. This study aimed to investigate the roles of protein arginine methyltransferase 6 (PRMT6) in gastric cancer. Immunohistochemistry was performed to detect PRMT6 expression in gastric tumors. Real-time transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to detected mRNA levels. Protein expression was determined using western blot. Gastric cancer cells were co-cultured with CD8+ T cells. Colony formation assay was performed to detect cell proliferation. Flow cytometry was performed to determine CD8+ T cell function and tumor cell apoptosis. PRMT6 was overexpressed in gastric tumors. High level of PRMT6 predicted poor outcomes of gastric cancer patients and inhibition of CD8+ T cell infiltration. PRMT6 promoted proliferation of CD8+ T cells and enhanced its tumor killing ability. Moreover, PRMT6 upregulated annexin A1 (ANXA1) and promoted ANXA1 protein stability. ANXA1 overexpression suppressed the proliferation of CD8+ T cells and promoted tumor cell survival. PRMT6 functions as an oncogene in gastric cancer. PRMT6-mediated protein stability inhibits the infiltration of CD8+ T cells, resulting in immune evasion of gastric cancer. The PRMT6-ANXA1 may be a promising strategy for gastric cancer.

Osteosarcoma (OS) is a malignant bone carcinoma that affects people in childhood and adulthood. The heterogeneous nature and chromosomal instability represent certain characteristics of OS cells. These cancer cells grow and migrate abnormally, making the prognosis undesirable for patients. Conventional and current treatments fail to completely eradicate tumor cells, so new therapeutics targeting genes may be considered. PI3K/Akt is a regulator of events such as growth, cell death, migration, and differentiation, and its expression changes during cancer progression. PTEN reduces PI3K/Akt expression, and its mutations and depletions have been reported in various tumors. Experimental evidence shows that there is upregulation of PI3K/Akt and downregulation of PTEN in OS. Increasing PTEN expression may suppress PI3K/Akt to minimize tumorigenesis. In addition, PI3K/Akt shows a positive association with growth, metastasis, EMT and metabolism of OS cells and inhibits apoptosis. Importantly, overexpression of PI3K/Akt causes drug resistance and radio-resistance and its level can be modulated by miRNAs, lncRNAs and circRNAs. Silencing PI3K/Akt by compounds and drugs can suppress OS. Here, we review in detail the function of the PTEN/PI3K/Akt in OS, revealing its biological function, function in tumor progression, resistance to therapy, and pharmacological significance.

Gastric cancer (GC) poses a significant threat to human health and remains a prevalent form of cancer. Despite clinical treatments, the prognosis for Gastric cancer patients is still unsatisfactory, largely due to the development of multidrug resistance. Oxaliplatin (OXA), a second-generation platinum drug, is commonly recommended for adjuvant and palliative chemotherapy in Gastric cancer; however, the underlying mechanisms of acquired resistance to Oxaliplatin in Gastric cancer patients are not yet fully understood. In this study, we aimed to explore the potential mechanisms of Oxaliplatin resistance in Gastric cancer by employing bioinformatics analysis and conducting in vitro experiments. Specifically, we focused on investigating the role of methyltransferase-like 3 (METTL3). Our findings revealed that the knockdown of METTL3 significantly impeded the proliferation and migration of Gastric cancer cells. METTL3 knockdown induced apoptosis in OXA-resistant Gastric cancer cells and enhanced their sensitivity to Oxaliplatin. Furthermore, we found that DNA repair pathways were significantly activated in OXA-resistant Gastric cancer cells, and METTL3 knockdown significantly inhibited DNA repair pathways. Another important finding is that METTL3 knockdown and OXA-induced Gastric cancer cell death are additive, and the targeted METTL3 can assist Oxaliplatin treatment. Collectively, our findings suggest that METTL3 knockdown can augment the sensitivity of Gastric cancer cells to Oxaliplatin by impeding DNA repair processes. Consequently, targeting METTL3 holds great promise as a viable adjuvant strategy in the treatment of Gastric cancer patients.