Migration Capabilities Of Cells Research Articles

Implication of protein post translational modifications in gastric cancer

Gastric cancer (GC) is one of the most common and highly lethal malignant tumors worldwide, and its occurrence and development are regulated by multiple molecular mechanisms. Post-translational modifications (PTM) common forms include ubiquitylation, phosphorylation, acetylation and methylation. Emerging research has highlighted lactylation and glycosylation. The diverse realm of PTM and PTM crosstalk is linked to many critical signaling events involved in neoplastic transformation, carcinogenesis and metastasis. This review provides a comprehensive overview of the impact of PTM on the occurrence and progression of GC. Specifically, aberrant PTM have been shown to alter the proliferation, migration, and invasion capabilities of GC cells. Moreover, PTM are closely associated with resistance to chemotherapeutic agents in GC. Notably, this review also discusses the phenomenon of PTM crosstalk, highlighting the interactions among PTM and their roles in regulating signaling pathways and protein functions. Therefore, in-depth investigation into the mechanisms of PTM and the development of targeted therapeutic strategies hold promise for advancing early diagnosis, treatment, and prognostic evaluation of GC, offering novel insights and future research directions.

Identification and validation of TSPAN13 as a novel temozolomide resistance-related gene prognostic biomarker in glioblastoma.

Glioblastoma (GBM) is the most lethal primary tumor of the central nervous system, with its resistance to treatment posing significant challenges. This study aims to develop a comprehensive prognostic model to identify biomarkers associated with temozolomide (TMZ) resistance. We employed a multifaceted approach, combining differential expression and univariate Cox regression analyses to screen for TMZ resistance-related differentially expressed genes (TMZR-RDEGs) in GBM. Using LASSO Cox analysis, we selected 12 TMZR-RDEGs to construct a risk score model, which was evaluated for performance through survival analysis, time-dependent ROC, and stratified analyses. Functional enrichment and mutation analyses were conducted to explore the underlying mechanisms of the risk score and its relationship with immune cell infiltration levels in GBM. The prognostic risk score model, based on the 12 TMZR-RDEGs, demonstrated high efficacy in predicting GBM patient outcomes and emerged as an independent predictive factor. Additionally, we focused on the molecule TSPAN13, whose role in GBM is not well understood. We assessed cell proliferation, migration, and invasion capabilities through in vitro assays (including CCK-8, Edu, wound healing, and transwell assays) and quantitatively analyzed TSPAN13 expression levels in clinical glioma samples using tissue microarray immunohistochemistry. The impact of TSPAN13 on TMZ resistance in GBM cells was validated through in vitro experiments and a mouse orthotopic xenograft model. Notably, TSPAN13 was upregulated in GBM and correlated with poorer patient prognosis. Knockdown of TSPAN13 inhibited GBM cell proliferation, migration, and invasion, and enhanced sensitivity to TMZ treatment. This study provides a valuable prognostic tool for GBM and identifies TSPAN13 as a critical target for therapeutic intervention.

The mechanism study of LncRNA AC012181.2 targeting HERPUD1 protein in regulating stromal stem cells participating in metabolic reprogramming for gastric cancer metastasis.

To investigate the role of long non-coding RNAs (lncRNAs) in the metabolic reprogramming of gastric cancer through their regulation of mesenchymal stem cells (MSCs) and HERPUD1 protein targets, aiming to elucidate mechanisms that could lead to novel therapeutic strategies. The RNA-seq was performed on BGC and hMSC-BGC cells to perform LncRNA screening. And we employed cell culture techniques using hMSC-BM and BGC823 cells, treated with various genetic interventions including siRNA and overexpression vectors. Techniques such as cell viability assays, quantitative PCR (qPCR), Western blotting, RNA pull-down and RNA-FISH were utilized to validate the interaction between lncRNA AC012181.2 and HERPUD1 protein. Flow cytometry were utilized to analyze the impacts of lncRNA AC012181.2 on gene and protein expression related to cancer metabolism. Additionally, a tumorigenic model in nude mice was used to observe the in vivo effects. Modulation of AC012181.2 in MSCs significantly affected the proliferation, migration, and invasion capabilities of BGC823 gastric cancer cells. Knockdown of AC012181.2 resulted in reduced tumor growth in mouse models, along with changes in key gene and protein expression levels associated with cancer metabolism. Overexpression of AC012181.2 showed the opposite effect, enhancing tumor growth and altering cellular behaviors and molecular expressions in favor of cancer progression. The lncRNA AC012181.2 is crucial for gastric cancer metabolic reprogramming by regulating HERPUD1 Protein. Targeting it offers a promising avenue to impact the tumor microenvironment and develop novel gastric cancer therapies.

Autocrine small extracellular vesicles induce tubular phenotypic transformation in diabetic nephropathy via miR-21-5p.

Diabetic nephropathy (DN) is one of the most common and serious microvascular complications associated with diabetes. DN is the leading contributor to the majority of cases of end-stage renal disease (ESRD). Small extracellular vesicles (sEVs) can transport various genetic materials to recipient cells. The objective of this study was to explore how sEVs released from HK-2 cells when stimulated by high glucose levels influence renal tubular phenotypic transformation through miR-21-5p. Both human and cell studies were utilized to explore the crosstalk between proximal renal tubules in DN. sEVs from plasma and cells were isolated using ultracentrifugation, and the differential expression of miR-21-5p in plasma sEVs from DN patients versus healthy controls was quantified using Quantitative Real-time PCR (RT-qPCR). A DN model was constructed by stimulating HK-2 cells with glucose. The expression of epithelial-mesenchymal transition (EMT) proteins in each cell group was analyzed by Western Blot (WB), while miR-21-5p levels in both cells and their sEVs were quantified using RT-qPCR. A stable transfected HK-2 cell line was constructed. The CCK8 assay, scratch assay, and WB were employed to detect EMT proteins, aiming to explore how autocrine sEVs affect tubular phenotypic transformation in diabetic nephropathy (DN). The expression of miR-21-5p in plasma sEVs was significantly elevated in the DN group compared to the healthy control group. High glucose (HG) stimulation of HK-2 cells resulted in higher miR-21-5p expression in both cells and their sEVs, leading to enhanced proliferation, migration, and EMT capacities in these cells. Co-incubation of HK-2 cells with HG-sEVs significantly enhanced the proliferation, migration, and EMT capabilities of the recipient cells, but miR-21-5p knockdown reversed these effects. These results indicate that high glucose stimulates HK-2 cells to secrete sEVs, which promote DN proliferation, migration, and EMT through miR-21-5p, thereby offering new insights into the treatment of DN.

Citrus maxima extract-coated versatile gold nanoparticles display ROS-mediated inhibition of MDR-Pseudomonas aeruginosa and cancer cells.

The expanding prevalence of microbial resistance to conventional treatments has triggered a race to develop alternative/improved strategies to combat drug-resistant microorganisms in an efficient manner. Here, the lethal impact of the biosynthesized gold nanoparticles (AuNPs) against multi-drug resistant (MDR) bacteria has been elucidated. AuNPs, synthesized from the extracts of the fruit, leaf and peel of the Citrus maxima plant, were physicochemically characterized by UV-Vis spectrophotometry, Dynamic Light Scattering (DLS), electron microscopy and spectroscopic techniques not only confirmed the production of AuNPs of size below 100nm but also identified the phytochemicals adsorbed onto the surface of NPs. AuFeNP not only showed excellent antioxidant activity (∼95% at 1mg/mL) but also exhibited a commendable antimicrobial activity against MDR-Pseudomonas aeruginosa as assessed by the zone of inhibition (13.5mm) and microwell broth dilution assays (9.5μg/mL, MIC). Transmission electron microscopy (TEM) displayed bacterial cell membrane destruction post-AuNPs exposure. The killing mechanism of AuNPs elucidated the permeabilization of the cell membrane and generation of reactive oxygen species (ROS), ∼10-fold high depletion of GSH, and eventually leaching protein out of the cell. DNA damage, as a marker of apoptosis, was also noticed, which could be an implication of ROS accumulation in MDR-PA. AuNPs displayed significant toxicity at∼10μg/mL on various cancer cells (HT-1080, MRC-5, MDA-MB-231 and B16-F10) and relatively low toxicity on normal cells (MRC-5 and HaCaT). Scratch assay to identify the migration capability of breast cancer cells on treatment with AuNPs deciphered hampering of migration potential of breast cancer cells. Apoptotic topographies in B16-F10 cells were confirmed using AO/EtBr dual dye staining, DNA fragmentation, Caspase-3 assay and cell cycle analysis using flow cytometry. Hemolysis revealed minimal toxicity of AuNPs on human red blood cells. Nominal toxicity (∼70% survival at 500μg/mL of AuNPs) on mammalian cells was evaluated using Cell Titer-Glo cell viability assay. Overall results advocate the promising potential of biosynthetic AuFeNP against multi-drug-resistant pathogens and for further formulation into anticancer agents.

A telomere-related signature for predicting prognosis and assessing immune microenvironment in osteosarcoma

ObjectiveOsteosarcoma is the most common primary bone cancer with a high propensity for local invasion and metastasis. An increasing number of research studies show that telomeres play an important role in the occurrence and development of cancer. Thus, we established a telomere-related signature in osteosarcoma to comprehensively evaluate the pathogenic roles of telomeres in this disease.MethodsThe data on osteosarcoma were collected from the TARGET and Gene Expression Omnibus databases. First, we constructed a telomere-related signature using univariate and LASSO Cox regression analyses. Subsequently, we analyzed the prognostic value, functional annotation, immune microenvironment, and cell communication patterns of the telomere-related signature in osteosarcoma via comprehensive bioinformatics analyses. Cell proliferation was analyzed using the CCK-8 assay, and cell migration and invasion capabilities were evaluated using the Transwell assay.ResultsBased on the SP110, HHAT, TUBB, MORC4, TERT, PPARG, MAP3K5, PAGE5, MAP7, and CAMK1G, a telomere-related signature was built in osteosarcoma patients. The telomere-related signature could effectively predict the prognosis of osteosarcoma patients. The osteosarcoma patients in the high TELscore group exhibited poor prognosis. In addition, the telomere-related signature demonstrated predictive value for the immune microenvironment and drug sensitivity in osteosarcoma. Finally, we discovered significant reduction in MAP7 expression in osteosarcoma cells, and patients with low MAP7 expression had poor prognosis. Moreover, the overexpression of MAP7 significantly reduced cell proliferation, the ability of cell migration, and invasion in osteosarcoma cells.ConclusionA telomere-related signature was constructed in osteosarcoma patients, offering predictive values into prognosis, the immune microenvironment, and drug sensitivity. Moreover, MAP7 might serve as a prognostic marker for osteosarcoma patients.

Relationship between transmembrane emp24 domain containing 2 expression and tumor stem cell characteristics in oral cancer

Objective: Transmembrane Emp24 Domain Containing 2 (TMED2) is a mediator of membrane protein trafficking involved in intracellular protein transport. Recent research suggests that TMED2 plays an important role in the development and metastasis of tumors; however, its exact mechanisms in oral cancer (OC) remain unclear. This study aims to elucidate the role and possible mechanisms of TMED2 in OC. Material and Methods: We investigated the impact of TMED2 knockdown on the invasion, migration, and proliferation capabilities of OC cells. Furthermore, we analyzed the in vitro and in vivo interactions between TMED2 and polypeptide-N-acetylgalactosaminyltransferase 7 (GALNT7) as well as explored the regulatory function of TMED2 on GALNT7. The alterations in stem cell markers were assessed using clone formation assays, western blot, and quantitative real-time polymerase chain reaction. Results: The upregulation of TMED2 promoted the proliferation and invasion abilities of OC cells. Further analysis revealed that TMED2 enhanced the stem-like properties and tumorigenicity of OC cells by directly regulating the expression of GALNT7. In vivo and in vitro results suggested that silencing TMED2 expression reduced the incidence of OC. Conclusion: Our data imply that TMED2 stimulates GALNT7 transcription, which in turn amplifies the stem-like characteristics and carcinogenic potential of OC cells. Moreover, the block of TMED2 prevents cancers from growing and spreading in vivo. This finding provides a new therapeutic target for the treatment of OC and highlights the critical role of TMED2 in the condition.

M1A-regulated DIAPH3 promotes the invasiveness of colorectal cancer via stabilization of KRT19

BackgroundIn recent years, the emphasis has shifted to understanding the role of N1-methyladenosine (m1A) in tumor progression as little is known about its regulatory effect on mRNA and its role in the metastasis of colorectal cancer (CRC).MethodsWe performed methylated RNA immunoprecipitation sequencing of tumor tissues and tumor-adjacent normal tissues from three patients with CRC to determine the m1A profile of mRNA in CRC. The expression of diaphanous-related formin 3 (DIAPH3) and its correlation with clinicopathological characteristics of CRC were evaluated using immunohistochemistry and online datasets. The role of DIAPH3 in the migration and invasion of CRC cells was evaluated using wound healing assay, Transwell assay and xenograft metastatic model. The downstream targets of DIAPH3 were screened using mass spectrometry. By co-transfecting DIAPH3 siRNA and a keratin 19 (KRT19) ectopic plasmid into CRC cells, the role of DIAPH3-KRT19 signaling axis was confirmed.ResultsThe mRNA level of DIAPH3 and its m1A modifications increased simultaneously in the CRC tissues. In addition, high DIAPH3 expression in CRC tissues is significantly associated with metastasis and progression to an advanced stage. After the knockdown of DIAPH3, the migration and invasion capabilities of CRC cells suffered a notable decline, which could be rescued by overexpressing KRT19. In addition, the proteasome inhibitor MG132 could block the degradation of KRT19 induced by DIAPH3 silencing.ConclusionsOur study reveals that DIAPH3 mRNA was modified in CRC cells by m1A methylation. Silencing DIAPH3 suppresses the migration and invasion of CRC cells, potentially through the proteasome-dependent degradation of downstream KRT19.

Mechanistic Insights into the Inhibition of Colorectal Cancer by BuShenFang through Adenomatous Polyposis Coli Expression and Wnt/β-catenin Pathway Regulation

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. Despite advances in chemotherapy and radiotherapy, significant side effects persist, prompting the exploration of alternative therapies such as traditional Chinese medicine (TCM). BuShenFang (BSF), a TCM formulation, is believed to exhibit anti-CRC effects, although its exact mechanism is unclear. This study aims to investigate the effects of BSF on CRC cells through the modulation of the Wnt/β-catenin pathway. The study utilized HCT116 and SW620 CRC cell lines, employing in vitro experiments including cell viability assays, colony formation, flow cytometry, and Western blot to examine the influence of BSF on cellular proliferation, apoptosis, migration, and the Wnt/β-catenin signaling pathway. Results demonstrated that BSF significantly inhibited the proliferation of CRC cells in a dose-dependent manner. The apoptotic rate was markedly increased in the 20% BSF group, while colony formation, migration, and invasion capabilities of CRC cells were notably suppressed. Furthermore, Western blot results revealed that BSF enhanced adenomatous polyposis coli (APC) expression and inhibited β-catenin, c-Myc, and Cyclin D1, key proteins in the Wnt/β-catenin pathway. In conclusion, BSF exerts anti-CRC effects by modulating the Wnt/β-catenin pathway, suggesting its potential as a complementary therapeutic agent in CRC treatment. Future studies should focus on in vivo models to validate these findings.

Donafenib activates the p53 signaling pathway in hepatocellular carcinoma, induces ferroptosis, and enhances cell apoptosis

Donafenib is an improved version of sorafenib in which deuterium is substituted into the drug’s chemical structure, enhancing its stability and antitumor activity. Donafenib exhibits enhanced antitumor activity and better tolerance than sorafenib in preclinical and clinical studies. However, the specific mechanism of its effect on hepatocellular carcinoma has not been reported. Iron deposition is a cell death pattern caused by disturbances in iron metabolism. Apoptosis is a form of programmed cell death. They may interact with each other during cell death. This study mainly explores the potential mechanism of donafenib activating the p53 signaling pathway, inducing iron deposition, and enhancing cell apoptosis in hepatocellular carcinoma. Hepa1-6 and Huh7 cells were treated with various concentrations of donafenib. Scratch healing and pore migration tests were conducted. Analyze apoptosis through flow cytometry and TUNEL fluorescence labeling. RNA sequencing was conducted on both untreated and donafenib-treated Huh7 cells. The key proteins involved in ferroptosis (SLC7A11, GPX4) and apoptosis (caspase3, caspase8, Bax, Bcl-2, p53) were then evaluated using immunoblotting and immunohistochemical staining. Reactive oxygen species (ROS) levels in the cancer cells were measured. Donafenib treatment resulted in a dose-dependent decrease in the proliferation, migration, and invasion capabilities of cancer cells. There was an increase in apoptosis rates and ROS accumulation, and a reduction in tumor volume. The key proteins involved in ferroptosis and apoptosis underwent significant changes. Donafenib activates the p53 signaling pathway, induce ferroptosis, and enhance apoptosis, suggesting its potential as an effective therapeutic agent for HCC.

Identification of EARS2 as a Potential Biomarker with Diagnostic, Prognostic, and Therapeutic Implications in Colorectal Cancer.

Colorectal cancer (CRC) is a prevalent malignancy, and lactate metabolism significantly influences tumorigenesis and progression. This study identifies key genes associated with lactic acid metabolism and explore their impact on CRC. This study utilized data from The Cancer Genome Atlas, Gene Expression Omnibus, other public databases, and our institutional resources. Machine learning identified key lactate metabolism-related genes. Receiver Operating Characteristic analysis, Kaplan-Meier analysis, and the construction of a nomogram model were conducted to assess the diagnostic and prognostic significance of the key lactate metabolism-related gene EARS2. EARS2 expression in colorectal tissue was validated using both publicly available external data and samples from our institution. To investigate the mechanisms underlying EARS2 in CRC, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment Analysis, and Protein-Protein Interaction analyses were performed, alongside the construction of miRNA-mRNA interaction networks. Additionally, the relationships between EARS2 and immune cell infiltration, as well as responses to drug therapy, were examined. Following the knockdown of EARS2, we assessed cell proliferation, migration capabilities, and apoptosis. Statistical analyses were conducted using R and GraphPad Prism software. ERAS2 was overexpressed in CRC tissues compared to normal and adenoma tissues, with higher expression levels correlating with aberrant lactate metabolism and poorer patient prognosis. EARS2 was involved in pathways such as neuroactive ligand-receptor interactions, protein digestion, and cholesterol metabolism, and it was associated with immune cell infiltration and responses to drug treatment. Additionally, the knockdown of EARS2 inhibited the proliferation, migration, and invasion of CRC cells while enhancing their apoptosis. Elevated expression of EARS2 is associated with abnormal lactate metabolism, immune cell infiltration, altered therapeutic sensitivity, and poorer survival outcomes in CRC. This correlation suggests that EARS2 may serve as a potential target for the diagnosis, prognosis, and therapeutic intervention in CRC.

Lnc-EST885 promotes hepatocellular carcinoma metastasis through PI3K / AKT pathway by interaction with TRAF4.

Hepatocellular carcinoma (HCC) represents a major malignancy globally, characterized by high malignancy and intricate molecular mechanisms. This study aims to explore the role of the long non-coding RNA (lncRNA) lnc-EST885 in HCC development. Cell experiments including FISH, western blot, flow cytometry and functional analysis were used to elucidate the effects of lnc-EST885 on cell proliferation, apoptosis, migration and EMT processes. RNA pull-down and ESI-FT-ICR-MS were used to identify proteins that interact with lnc-EST885 and were verified by RIP-qPCR. Furthermore, the association of lnc-EST885 and TRAF4 with HCC prognosis and metastasis was evaluated through bioinformatics analysis and animal models. lnc-EST885 is one of the lncRNAs with the highest expression levels in M2-type macrophages. The expression of lnc-EST885 in HCC tissues is significantly higher than in normal tissues, and high expression is associated with poor prognosis. Functional experiments have shown that lnc-EST885 significantly promotes the proliferation and migration of liver cancer cells, inhibits apoptosis, and induces EMT. Studies in a mouse lung metastasis model have also confirmed that lnc-EST885 promotes the pulmonary metastasis of HCC cells in vivo. Mechanistic studies have revealed that lnc-EST885 can bind to the TRAF4 protein, activating the PI3K/AKT signaling pathway, thereby promoting the proliferation, migration, and EMT capability of liver cancer cells, contributing to the malignant phenotype of HCC. lnc-EST885 plays a crucial role in the development of liver cancer, serving as a potential biomarker for predicting HCC prognosis and providing a new target for HCC treatment.

Identification of the Roles of Coagulation-related Signature and its Key Factor RABIF in Hepatoma Cell Malignancy.

Hepatoma is a high morbidity and mortality cancer, and coagulation is a potential oncogenic mechanism for hepatoma development. In this study, we aimed to reveal the role of coagulation in hepatoma. We applied the LASSO to construct a coagulation-related risk score (CRS) and a clinical nomogram with independent validation. The heterogeneity of various aspects, including functional enrichment, SNV, CN, immunocyte infiltration, immune pathways, immune checkpoint, and genomic instability indexes, was evaluated. Besides, the prognostic value of the CRS genes was tested. We selected the critical risky gene related to coagulation from the LASSO coefficients, for which we applied transwell and clone formation assays to confirm its roles in hepatoma cell migration and clone formation ability, respectively. The CRS and the nomogram predicted patients' survival with good accuracy in both two datasets. The high-CRS group was associated with higher cell cycle, DNA repair, TP53 mutation rates, amplification, and lower deletion rates at chromosome 1. For immunocyte infiltration, we noticed increased Treg infiltration and globally upregulated immune checkpoints and genomic instability indexes. Additionally, every single CRS gene affected the patient's survival. Finally, we observed that RABIF was the riskiest gene in the CRS. Its knockdown suppressed hepatoma cell migration and clone formation capability, which could be rescued by RABIF overexpression. We built a robust CRS with great potential as a prognosis and immunotherapeutic indicator. Importantly, we identified RABIF as an oncogene, promoting hepatoma cell migration and clone formation, revealing underlying pathological mechanisms, and providing novel therapeutic targets for hepatoma treatment.

GCNT3 promotes the proliferation, apoptosis, invasion, and migration of breast cancer through the PI3K/AKT pathway.

Breast cancer (BRCA) constitutes one of the principal causes of death among women. The objective of this study was to explore the impact of glucose-aminotransferase 3 (GCNT3) on the growth, invasion, and metastasis of BRCA cells. Additionally, the aim of this research was to clarify the underlying molecular mechanisms through which GCNT3 influences the development and progression of BRCA and to ascertain the potential of GCNT3 as a novel BRCA biomarker. Analysis involved data sourced from the The Cancer Genome Atlas database (TCGA). Expression levels of GCNT3 were measured using Western blot analysis and immunohistochemistry (IHC). Additionally, cell functionality tests were performed posttransfection with GCNT3-specific interference plasmids to assess the influence of GCNT3 in BRCA by using EdU assay, transwell assay, and flow cytometric assay, as well as PI3K/AKT signaling pathway. GCNT3 levels were notably elevated in BRCA tissues compared to adjacent noncancerous tissues. Reducing GCNT3 expression significantly diminished the proliferation, invasion, and migration capabilities of BRCA cells (P<0.05) and concurrently increased apoptosis (P<0.05). The data also indicated that GCNT3 may be involved in activating the PI3K/AKT signaling pathway. Elevated GCNT3 expression in BRCA tissues suggests the potential of GCNT3 to be a biomarker for predicting BRCA prognosis. The regulation of p-PI3K and p-AKT levels by GCNT3 appears to considerably inhibit BRCA cell development and progression.

Role of early growth response-1 as a tumor suppressor in oral squamous cell carcinoma

BackgroundOral squamous cell carcinoma (OSCC) exhibits pronounced local invasiveness and a propensity for lymph node metastasis. Given its frequent detection at advanced stages and the consequential postoperative functional impairments, the identification of effective molecular markers for early detection and treatment is imperative. Early growth response-1 (EGR-1) serves as a versatile transcription factor expressed across various cell types. Its role in cancer is contentious, acting as either an oncogene or a tumor suppressor gene.MethodsThis study undertook comprehensive analyses, including big data scrutiny, expression profiling using 50 OSCC samples, and in vitro functional assessments, to elucidate EGR-1’s involvement in OSCC.ResultsComparative analysis revealed significantly reduced EGR-1 expression in oral cancer tissues compared to healthy controls or normal oral mucosa. In vitro experimentation with multiple OSCC cell lines demonstrated that EGR-1 curbed cell proliferation, migration, and invasion capabilities. Additionally, it was observed that EGR-1 prompted G0/G1 arrest in OSCC cells by modulating the activity of cell cycle regulators.ConclusionsThese findings strongly support EGR-1’s tumor-suppressive role in OSCC and hint at the potential for novel OSCC therapies aimed at restoring aberrant EGR-1 function.

METTL3/YTHDF1 stabilizes CORO6 expression promoting osteosarcoma progression through glycolysis

This study investigates the role of CORO6 (Coronin 6) in the development of osteosarcoma. Osteosarcoma is a common malignant bone tumor in children and adolescents, characterized by rapid and irregular bone growth and a high risk of distant lung metastasis. CORO6 is a member of the Coronin family, known for its conserved WD40 repeat domain. This structure allows CORO6 to inhibit actin dynamics through interactions with F-actin and Arp2/3, thereby affecting the organization of the cytoskeleton. Our research found that in osteosarcoma patients, the levels of CORO6 are significantly elevated. Experimental observations showed that reducing the expression of CORO6 significantly inhibits the growth, migration, and invasion abilities of osteosarcoma cells. Moreover, in vivo experiments demonstrated that the absence of CORO6 effectively inhibits the growth of osteosarcoma in animal models. We also discovered that CORO6 promotes the proliferation, migration and invasion capabilities of osteosarcoma cells by activating the Wnt/β-catenin signaling pathway. Moreover, CORO6 plays a critical important role in glycolysis of osteosarcoma cells. Mechanically, we found that METTL3/YTHDF1 induced m6A modification of CORO6 mRNA promoted the expression of CORO6 by enhancing its stability. These findings offer new directions for the treatment of osteosarcoma, suggesting that CORO6 could be a novel prognostic biomarker and an effective therapeutic target for patients.In summary, CORO6, as an oncogene, plays a key role in the development of osteosarcoma, providing a crucial theoretical basis for the development of new osteosarcoma treatment strategies.

A new tumor-treating device OM-100 with low-frequency magnetic fields inhibits proliferation and metastasis in liver cancer

BackgroundThis study aims to investigate a novel instrument OM-100 with low-frequency magnetic fields (LFMFs) for its potential applicability in the treatment of liver cancer.MethodsLiver cancer cell lines (HepG2 and Huh7) and normal liver cell line THLE-2 were exposed to OM-100 at LFMFs of 0, 10, 25, 50, and 100 kHz for 2 h in the morning, noon, and evening, respectively. The effects of LFMF on cell viability, apoptosis, migration, and invasion capabilities were examined. Additionally, impacts of LFMF on ROS production was assessed. In vivo studies were conducted to examine the safety profile of OM-100 and its effects on tumor growth.ResultsIn vitro, OM-100 reduced the viability of liver cancer cells, increased cell apoptosis, and inhibited cell migration and invasion abilities in a frequency-dependent manner (P < 0.05). In vivo, OM-100 significantly slowed down tumor growth and promoted apoptosis in liver tumors (P < 0.05). Moreover, OM-100 rarely affected the viability of normal liver cells, as well as the health of normal mice. Finally, we further found that OM-100 significantly increased the production of ROS in liver cancer cells (P < 0.05), a key factor in inducing autophagy, which is very important for the progression of liver cancer.ConclusionOur findings reveal the safety of OM-100 and its frequency at 100 kHz significantly inhibits liver cancer progression.

RIPK2 and lysosomal pathway: Unveiling a new mechanism for lung cancer metastasis

BackgroundThis study aims to explore the role of RIPK2 in lung cancer metastasis and its potential mechanisms. MethodsThe expression levels of RIPK2 in lung cancer patients and cell lines were detected by immunohistochemistry, qRT-PCR, and Western blot. RIPK2 expression was knocked down using siRNA technology, and its effects on the proliferation, migration, and invasion capabilities of lung cancer cells were assessed through CCK-8, EdU, colony formation, and Transwell assays. Furthermore, by overexpressing RIPK2 and LAMP2, the regulatory effect of RIPK2 on the lysosomal pathway and its mechanism of action in lung cancer metastasis were investigated. ResultsThe results showed that the expression of RIPK2 was significantly increased in lung cancer patients and cell lines. Knockdown of RIPK2 significantly inhibited the migration, invasion, and proliferation capabilities of lung cancer cells, while overexpression of RIPK2 promoted these malignant behaviors. Further studies found that RIPK2 promoted lung cancer metastasis by inhibiting LAMP2 expression, thereby suppressing the lysosomal pathway and altering the tumor microenvironment. Additionally, overexpression of LAMP2 could reverse the promotive effects of RIPK2 overexpression on the malignant behaviors of lung cancer cells. ConclusionThis study reveals for the first time that RIPK2 promotes lung cancer metastasis by inhibiting LAMP2 expression, thereby suppressing the lysosomal pathway and altering the tumor microenvironment. In the future, targeted therapy against RIPK2 and LAMP2 may become an effective means to inhibit lung cancer metastasis.

Biophysical and Morphological Cell Features Retrieved by Digital Holographic Microscopy Correlate with Drug-Induced Changes in Cell Migration Behavior.

Quantitative analysis of cancer cell migration is critical for developing effective therapies to curb cancer metastasis. However, traditional methods are time-consuming and labor-intensive and lack quantitative capabilities. Cell volume change, a key physiological indicator of cell migration, is directly linked to phase change. In this work, we have developed a model that connects phase features from digital holographic microscopy (DHM) with cell healrate values from the wound healing assay. This approach aims to provide a rapid and quantitative evaluation of the breast cancer cell migration capability. Using DHM, six phase features of 231 cells treated with varying drug concentrations were extracted. It was observed that the rate of change of these phase features, termed characteristic parameters, showed a high linear correlation with cell healrate values from wound healing assays. Based on these linear correlations, a composite coefficient was derived by linearly combining the characteristic parameters of the six phase features. This composite coefficient was then linearly correlated with the cell healrate values to create a correlation model. This model establishes a strong connection between DHM-extracted morphological/biophysical features and cell migration metrics from a complementary assay. It provides a new, rapid, and quantitative method for assessing cancer cell migration in vitro and delivering valuable insights for cancer research.

Jing-Si herbal tea attenuates oral cancer cell viability, migration, and invasion by regulating epithelial-to-mesenchymal transition and reactive oxygen species accumulation

IntroductionOral cancer is the sixth most common cancer worldwide and can be life-threatening if not diagnosed and treated in its early stages. Jing-Si herbal tea (JSHT), containing eight traditional Chinese medicine-based herbs, is known to suppress the malignancy, growth, and metastasis of several tumour cells, including breast, lung, and colon cancer cells. However, the pharmacological effect of JSHT on oral cancer progression is still unclear. MethodsIn this study, we evaluated the potential of JSHT to arrest the development of oral cancer via induction of cell death by reactive oxygen species (ROS) accumulation and inhibition of migration, invasion, and epithelial-to-mesenchymal transition (EMT). For this purpose, we employed the human tongue squamous cell carcinoma human tongue squamous carcinoma cell line, which we treated with different JSHT concentrations for 24 hours, and assessed cell viability, migration, and wound healing capabilities, together with western blotting for measuring expression levels of EMT markers. ResultsSurvival, migration/invasion ability, EMT, and ROS production in the human tongue squamous carcinoma human tongue squamous carcinoma and FaDu human pharynx squamous cell carcinoma cell line were decreased by JSHT treatment via Lon protease-independent mechanisms. ConclusionThis study demonstrates that JSHT could be regarded as a candidate new supplement to existing anticancer therapies and an alternative, orally administered healthcare product for treating oral squamous cell carcinoma.