Invasion Ability Research Articles

Vulnerability of Antioxidant Drug Therapies on Targeting the Nrf2-Trp53-Jdp2 Axis in Controlling Tumorigenesis.

Control of oxidation/antioxidation homeostasis is important for cellular protective functions, and disruption of the antioxidation balance by exogenous and endogenous ligands can lead to profound pathological consequences of cancerous commitment within cells. Although cancers are sensitive to antioxidation drugs, these drugs are sometimes associated with problems including tumor resistance or dose-limiting toxicity in host animals and patients. These problems are often caused by the imbalance between the levels of oxidative stress-induced reactive oxygen species (ROS) and the redox efficacy of antioxidants. Increased ROS levels, because of abnormal function, including metabolic abnormality and signaling aberrations, can promote tumorigenesis and the progression of malignancy, which are generated by genome mutations and activation of proto-oncogene signaling. This hypothesis is supported by various experiments showing that the balance of oxidative stress and redox control is important for cancer therapy. Although many antioxidant drugs exhibit therapeutic potential, there is a heterogeneity of antioxidation functions, including cell growth, cell survival, invasion abilities, and tumor formation, as well as the expression of marker genes including tumor suppressor proteins, cell cycle regulators, nuclear factor erythroid 2-related factor 2, and Jun dimerization protein 2; their effectiveness in cancer remains unproven. Here, we summarize the rationale for the use of antioxidative drugs in preclinical and clinical antioxidant therapy of cancer, and recent advances in this area using cancer cells and their organoids, including the targeting of ROS homeostasis.

Corosolic acid inhibits EMT in lung cancer cells by promoting YAP-mediated ferroptosis

BackgroundCorosolic acid (CA), a naturally occurring pentacyclic triterpenoid is renowned for its anticancer attributes. Previous studies have predominantly centered on the anticancer properties of CA in lung cancer, specifically its role in inducing apoptosis, however, investigations regarding its involvement in ferroptosis have been scarce. MethodsThe apoptotic and proliferative effects were evaluated by CCK8 and colony formation assay. Cell death and ROS generation were measured to assess the response of CA to iron death induction. Scratch and invasion assays were performed to verify the effect of CA on the invasive ability of lung cancer cells. Protein and mRNA expression were analyzed using Western blotting and qPCR. The CHX assay was carried out to detect protein half-life. Metabolite levels were measured with appropriate kits. Protein expression was detected through IF and IHC. A xenograft tumor model was established to investigate the inhibitory effect of CA on lung cancer in vivo. ResultsThe current findings revealed that CA exerts its anticancer effect by inducing cell death, accompanied by the accumulation of lipid reactive oxygen species (ROS), hinting at the possible involvement of ferroptosis. Our experimental results further substantiated the significance of ferroptosis in the CA anticancer mechanism, as ferroptosis inhibitors were found to effectively rescue CA-induced cell death. Significantly, we demonstrated for the first time that CA could induce ferroptosis further by suppressing EMT in lung cancer cells. Additionally, CA could regulate GPX4 to induce ferroptosis, interestingly, CA downregulated GSH synthetase by inhibiting YAP rather than GPX4, thereby reducing GSH, inducing ferroptosis, and further suppressing EMT in lung cancer cells.We also discovered that GSS is a crucial downstream target of YAP in regulating GSH. Moreover, a xenograft mouse model indicated that CA could trigger ferroptosis in lung cancer cells by regulating YAP expression and GSH levels. ConclusionCA inhibited lung cancer cell metastasis by inducing ferroptosis. Our data offer the first evidence that CA induces ferroptosis in lung cancer cells by regulating YAP/GSS to modulate GSH, thereby further suppressing EMT. These results imply the potential of CA as an inducer of ferroptosis to inhibit lung cancer metastasis.

Anti-Cancer Activity and Mechanism of Resveratrol Against Triple-Negative Breast Cancer

This research analyzed the antitumor of resveratrol in triple negative breast cancer (TNBC). TNBC were divided into control group and resveratrol group. Tnbc-associated TNBC cells were stimulated by different concentrations of resveratrol, and the proliferation, apoptosis, migration of the cells were analyzed. The amount of migration was measured by Transwell method. The PI3K, Akt, and mTOR were detected. Results showed that the cell apoptosis was obvious and the invasion ability was decreased in resveratrol group, and the effect was more obvious with the increase of dosage, and there was a statistical difference between groups (P < 0.05). Resveratrol significantly decreased the expression of Akt, PI3K and mTOR, and there were statistical differences between groups (P < 0.05). In summary, resveratrol reduces cell migration, promotes cell apoptosis, inhibits cell proliferation, and its mechanism is closely related to the blocking of PI3K/Akt/mTOR.

The inhibition effect of psoralen on prostate cancer PC3 cells via down-regulation of long non-coding RNA ENST00000510619.

New medications are needed to improve outcomes of castration-resistant prostate cancer (CRPC). Psoralen has been reported to have anti-cancer properties for various tumors, but there are limited reports about psoralen treatment in prostate cancer (PCa). This study aimed to investigate the effect of psoralen on PC3 cells and to investigate potential underlying mechanisms of action. The effect of psoralen on the proliferation and cell cycle progression of PC3 cells was determined using Cell Counting Kit-8 (CCK-8) test and flow cytometry, respectively. The differential gene profiles in PC3 cells treated with psoralen were determined with microarray analyses. The effect of psoralen on long non-coding RNA (lncRNA) ENST00000510619 expression in PC3 cells was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The effect of psoralen and transfection of small interfering lnc-RNA (si-lncRNA) ENST00000510619 on cell viability, invasion ability, and migratory activity of PC3 cells were evaluated using the CCK-8 test, transwell assay, and wound healing, respectively. Psoralen significantly inhibited PC3 cells in a concentration- and time-dependent manner and caused G1 phase and G2/M phase cycle arrests. When screened with a fold change (FC) of ≥2 and a P value of <0.05, 1,716 lncRNAs and 1,160 messenger RNAs (mRNAs) were significantly up-regulated, whereas 3,269 lncRNAs and 3,263 mRNAs were significantly down-regulated in PC3 cells after psoralen treatment. Among the differentially down-regulated lncRNAs in which the signal of the probe showed significant differences compared to the background, lncRNA ENST00000510619 had the highest FC. The expression of lncRNA ENST00000510619 was shown to be down-regulated by psoralen in a concentration-dependent manner. CCK-8 assay, wound healing, and transwell assay showed that both psoralen and si-lncRNA ENST00000510619 transfection significantly inhibited the activity, invasion, and migration of PC3 cells (P<0.01 for all). Psoralen was confirmed to inhibit proliferation and block the cell cycle in PC3 cells in this in vitro study. The molecular mechanism involves multiple differentially expressed lncRNAs and mRNAs and is related to the down-regulation of lncRNA ENST000000510619 expression. This study provides the experimental basis for the development of psoralen as a novel anti-CRPC drug and for the consideration of lncRNA ENST00000510619 as a potential clinical target for CRPC.

Tinglu Yixin granule inhibited fibroblast-myofibroblast transdifferentiation to ameliorate myocardial fibrosis in diabetic mice

Ethnopharmacological relevanceMyocardial fibrosis is one of the pathological characteristics of advanced diabetic cardiomyopathy (DCM) and serves as the strong evidence of poor prognosis. Among them, the transdifferentiation of cardiac fibroblasts (CFs) may play a crucial role in the development of myocardial fibrosis in DCM. Tinglu Yixin granule (TLYXG) has been clinically used for many years and can significantly improve cardiac function of patients with DCM. However, the effect of TLYXG on myocardial fibrosis in DCM remains unknown, and the underlying mechanisms of its efficacy have yet to be fully understood. Aim of the studyThis study aimed to investigate the impact and underlying mechanism of TLYXG on myocardial fibrosis in diabetes mice. Materials and methodsThe bioactive compounds in TLYXG were identified using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). The potential mechanism of TLYXG in treating DCM was predicted using network pharmacology combined with molecular docking and protein-protein docking. The mice model of type 2 diabetes were established by intraperitoneal injection of streptozotocin (STZ) and the high-fat diet (HFD). Indicators of pancreatic islet function, lipids, oxidative stress, and inflammatory factors were tested using kits. Cardiac function was assessed in diabetic mice using echocardiography. Histologic staining was performed to evaluate myocardial hypertrophy and fibrosis. Mechanistically, the hypothesis was tested through rescue experiments. The expression levels of transient receptor potential channel 6 (TRPC6), transforming growth factor-β1 (TGF-β1), collagen I (COL-I) and alpha-smooth muscle actin (α-SMA), along with the mRNA and phosphorylation levels of SMAD family member 3 (Smad3) and protein 38 mitogen-activated protein kinase (p38 MAPK), were assessed using quantitative RT-qPCR, western blot, immunohistochemistry, and immunofluorescence. Neonatal lactating mice were used to extract primary CFs for vitro experiments. Scratch and transwell assays were conducted to assess CFs migration and invasion abilities. Western blot and immunofluorescence were used to evaluate the expression levels of CFs transdifferentiation markers COL-I and α-SMA. ResultsA total of 168 active ingredients were detected in TLYXG based on UPLC-MS and databases. Network pharmacology indicated that TLYXG could improve DCM through inflammatory mediator regulation of TRP channels, TGF-beta signaling pathway, and MAPK signaling pathway. ELISA results showed that TLYXG could ameliorate metabolic levels, inflammation, and oxidative stress in diabetic mice. Echocardiography suggested that TLYXG improved cardiac systolic and diastolic dysfunction in diabetic mice. Histological analysis revealed that TLYXG alleviated myocardial fibrosis in diabetes mice. Additionally, molecular docking analysis indicated strong binding activity between the main active ingredients of TLYXG and TRPC6 of the TRP family. At the molecular level, TLYXG reduced the mRNA and protein expression levels of TRPC6 and TGF-β1 and inhibited the mRNA and phosphorylation levels of Smad3 and p38 MAPK. Furthermore, TLYXG inhibited CFs migration and invasion, and reduced the expression levels of the CFs transdifferentiation markers COL-I and α-SMA. ConclusionTLYXG inhibited the proliferation, migration, invasion and transdifferentiation of CFs by suppressing TGF-β1/Smad3/p38 MAPK signaling through down-regulation of TRPC6, thereby ameliorating myocardial fibrosis in diabetes mice.

High expression of COL8A1 predicts poor prognosis and promotes EMT in papillary thyroid cancer.

Collagen type VIII α 1 chain (COL8A1), a collagen type VIII protein, has been suggested to exert various functions in progression of multiple cancers. However, the effect of COL8A1 in papillary thyroid cancer (PTC) has not been elucidated. The Cancer Genome Atlas (TCGA) databases were applied to investigate the COL8A1 expression and its clinical significance in PTC. The COL8A1 expression level was further validated using Gene Expression Omnibus (GEO) data and clinical paired PTC tissues. Additionally, Kaplan-Meier curve was used to analyze the prognosis. The cell migrative and invasive abilities were evaluated by wound healing assay and Transwell assay. CCK8 assays were used to evaluate proliferation of PTC cells. Western blotting was conducted to explore the potential mechanisms involved in the pro-tumor role of COL8A1. The correlation between immune cell infiltration and COL8A1 was analyzed using Tumor Immune Estimation Resource (TIMER) database and the single-sample GSEA (ssGSEA) method. We found that COL8A1 was upregulated in PTC (P<0.05). High COL8A1 expression level was significantly associated with advanced T stage (P<0.01), N stage (P<0.001) and poor prognosis (P=0.0142) in PTC. Furthermore, cell migration and invasion were significantly reduced following COL8A1 knockdown (P<0.001). Mechanistic studies demonstrated that the epithelial-to-mesenchymal transition (EMT) related proteins (FN1, MMP9, MMP7, ZEB2 and Twist1) and phosphorylation of AKT and ERK were obviously down-regulated after COL8A1 knockdown (P<0.01). Moreover, COL8A1 expression was correlated with immune cell infiltration. Our study demonstrates that COL8A1 may function as an oncogene and a potential prognostic biomarker for PTC patients.

MFGE8 promotes gastric cancer progression by activating the IL-6/JAK/STAT3 signaling

ObjectiveGastric cancer is malignant cancer with high morbidity and mortality worldwide. Milk fat globule EGF and factor V/VIII domain containing (MFGE8) was involved in many cancers. Nevertheless, the role of MFGE8 in gastric cancer remained indistinct. To probe the role of MFGE8 in gastric cancer and further explore the regulating mechanism. MethodsGEPIA was employed for analysis of MFGE8 expression and survival of gastric cancer patients. MFGE8 expression in gastric cancer was determined by immunohistochemistry, PCR, and western blot. The effect of MFGE8 on gastric cancer cells were evaluated by a series of cell function experiments. The mechanism of MFGE8 on gastric cancer was analyzed by GSEA and verified by in vitro and in vivo experiments. ResultsMFGE8 was over-expressed in gastric cancer. Silence of MFGE8 suppressed cell viability, proliferated ability, migrated and invasive ability, and EMT, but accelerated cell apoptosis. The opposite results were obtained in MFGE8-overexpressed gastric cancer cells. Zinc finger and BTB domain containing 7 A (ZBTB7A) was a transcription factor of MFGE8. ZBTB7A overexpression eliminated the effect of MFGE8 on gastric cancer cells. MFGE8 activated the IL-6/JAK/STAT3 signaling. Inhibition of IL-6/JAK/STAT3 signaling by Stattic (pathway inhibitor) could eliminate the promoting effect of MFGE8 on IL-6/JAK/STAT3 signaling. In addition, MFGE8 shRNA inhibited tumor growth. ConclusionMFGE8 promoted cell proliferation, EMT progress, and tumor growth of gastric cancer by activating the IL-6/JAK/STAT3 signaling.

PTGES is involved in myofibroblast differentiation via HIF-1α-dependent glycolysis pathway.

Lung cancer is the leading cause of cancer-related deaths worldwide. Patients with lung cancer usually exhibit poor prognoses and low 5-year survival rates. Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are both chronic lung dysfunctions resulting in lung fibrosis and increased risk of lung cancer. Myofibroblasts contribute to the progression of asthma, COPD and IPF, leading to fibrosis in the airway and lungs. A growing body of evidence demonstrates that metabolic reprogramming is a major hallmark of fibrosis, being important in the progression of fibrosis. Using gene expression microarray, we identified and validated that the lipid metabolic pathway was upregulated in lung fibroblasts upon interleukin (IL)-4, IL-13 and tumour necrosis factor (TNF)-α treatment. In this study, we described that prostaglandin E synthase (PTGES) was upregulated in lung fibroblasts after IL-4, IL-13 and TNF-α treatments. PTGES increased α-SMA levels and promoted lung fibroblast cell migration and invasion abilities. Furthermore, PTGES was upregulated in a lung fibrosis rat model invivo. PTGES increased AKT phosphorylation, leading to activation of the HIF-1α-glycolysis pathway in lung fibroblast cells. HIF-1α inhibitor or 2-DG treatments reduced α-SMA expression in recombinant PTGES (rPTGES)-treated lung fibroblast cells. Targeting PGE2 signalling in PTGES-overexpressing cells by a PTGES inhibitor reduced α-SMA expression. In conclusion, the results of this study demonstrate that PTGES increases the expression of myofibroblast marker via HIF-1α-dependent glycolysis and contributes to myofibroblast differentiation.

Actinidia chinensis polysaccharide interferes with the epithelial-mesenchymal transition of gastric cancer by regulating the nuclear transcription factor-κB pathway to inhibit invasion and metastasis.

To investigate the mechanisms of the effect of Actinidia chinensis polysaccharide (ACPS) on the invasion and metastasis of gastric cancer cells. BGC-823-Luc gastric cancer cells stably transfected with a luciferase gene were used to establish an insitutransplanted tumor mouse model. A live mouse imaging system was used to observe tumor growth, and hematoxylin and eosin staining was applied to analyze tissue histopathology. Transwell and scratch wound assays were performed to examine the invasive and migratory ability of BGC-823 cells. Immunofluorescence, confocal microscopy, immunohistochemistry, and Western blot assays were used to analyze the expressions of the nuclear transcription factor-κB (NF-κB) signaling pathway and epithelial-mesenchymal transition (EMT)-related proteins. ACPS significantly inhibited the growth of subcutaneously transplanted BGC-823-Luc gastric cancer tumors in nude mice and reduced inflammatory cell infiltration in tumor tissues. ACPS inhibited Epidermal Growth Factor-induced invasion, migration, and morphological changes in the cytoskeleton of BGC-823 cells. ACPS inhibited gastric cancer EMT and decreased the expression of matrix metallopeptidase 9, N-cadherin and p-NF-κB p65 in transplanted tumor tissues. ACPS inhibited the expression of matrix metalloproteinases and vascular adhesion factors in BGC-823 cells, promoted p65-NF-κB nuclear translocation, and regulated proteins associated with the NF-κB p65 pathway. ACPS inhibited gastric cancer invasion and metastasis both in vivo and in vitro, which evidenced the inhibition of gastric cancer EMT viaregulating the NF-κB inflammatory pathway.

Unlocking the Potential of Disulfidptosis-Related LncRNAs in Lung Adenocarcinoma: A Promising Prognostic LncRNA Model for Survival and Immunotherapy Prediction.

Disulfidptosis was stimulated in high SLC7A11 expression cells starving to glucose. We attempted to identify disulfidptosis-related lncRNAs (DRLs), built a prognostic model to predict survival, and analyzed the tumor microenvironment. The TCGA database was utilized to procure the pertinent data. By utilizing both Cox regression and the least absolute shrinkage and selection operator (LASSO) method, a risk model based on DRLs was formulated for prognostic evaluation. The ability of survival prediction was validated by multiple approaches. The biological functions were screened through GO, KEGG, and GSEA. Various methods were employed to evaluate the tumor immune environment, which included ESTIMATE, tumor mutation burden (TMB) score, CIBERSORT algorithm, and tumor immune dysfunction and exclusion (TIDE) score. Ninety-one DRLs were recognized, and lncRNA AC092718.4, AL365181.2, AL606489.1, EMSLR, and ENTPD3-AS1 were involved in the risk model. The GEO database was used to verify the influence of these lncRNAs on survival. The following analyses showed that survival could be predicted excellently by the DRLs risk model. The results of enrichment analyses pointed toward the involvement of the cell cycle and IgA production pathways. In the low-risk patient group, there was a notable surge in stromal, immune, and ESTIMATE scores, while the TMB scores took a tumble. Conversely, the high-risk patient group displayed a converse trend. Notably, the group of patients with lower risk scores and higher TMB scores showed the most favorable survival outcomes, underscoring the importance of considering both risk score and TMB in predicting the response to immune checkpoint blockade therapy. Furthermore, patients classified as high-risk might display resistance to both chemotherapy and targeted therapy. Cellular biological experiments proved that lncRNA AC092718.4 promoted invasion, migration, and proliferation abilities invitro. These results provided valuable insights into the role of DRLs in LUAD and presented a possible effective treatment approach for LUAD. We developed a disulfidptosis-related risk model with 5 lncRNAs that enables survival prediciton for LUAD patients and aids cilinical decisions by forecasting the TME, TMB, and drug sensitivity, making it a valuable tool for outcomes prediction.

BZW2 is a potential regulator of non-small cell lung cancer progression

BackgroundPersonalized targeted therapy has become an important strategy for cancer treatment owing to its remarkable therapeutic efficacy and safety. However, drug resistance remains the primary cause of treatment failure. Basic leucine zipper and W2 domain 2 (BZW2), which is aberrantly expressed in cancer, has been implicated in tumor progression and may serve as a new therapeutic target. Therefore, the role of BZW2 in non-small cell lung cancer (NSCLC) requires further investigation. MethodsThe expression and genetic alterations of BZW2 in pan-cancers were explored using The Cancer Genome Atlas (TCGA) PanCancer databases. The mRNA and protein levels of BZW2 in patients with NSCLC were verified in our cohort. Functional experiments including CCK8, colony formation, and transwell assays were performed to evaluate the impact of BZW2 on the proliferative, migratory, and invasive capacities of SK-MES-1 cells. Gene Set Enrichment Analysis was used to identify underlying biological processes and pathways. Single-cell RNA (scRNA) sequencing data were employed to investigate the tumor microenvironment of NSCLC and the co-expression of BZW2 and stemness-related genes. ResultsDysregulated BZW2 expression was observed in various malignant tumors. BZW2 expression was found to be significantly elevated in NSCLC. BZW2 depletion inhibited the growth, mobility, and invasive abilities of lung squamous cell carcinoma SK-MES-1 cells. BZW2 may be related to signaling pathways such as nucleotide excision repair, ubiquitin-mediated proteolysis, and the P53 signaling pathway. Biological processes, including translational initiation, tRNA processing, and RNA methylation, were observed to be enriched in the high-BZW2 group. Furthermore, there was a positive correlation between BZW2 and the m6A- and m5C-related genes. scRNA analysis revealed a co-expression relationship between BZW2 and stemness-related genes such as CD44, SOX9, and CD133. ConclusionsElevated BZW2 expression is associated with the proliferation, migration, and invasion of NSCLC, and BZW2 may be a potential therapeutic target for NSCLC.

Niraparib Enhances and Synergizes with Ganglioside GD2 to Potentiate its Inhibitory Effect on Bladder Cancer Cells.

This study aimed to study the inhibitory effect of niraparib alone or in combination with GD2 specific antibody on Bladder Cancer (BCa). The migration ability of BCa cells was assessed through a scratch assay. CCK-8 assay was performed to evaluate the viability of BCa cells, and Transwell invasion assays were utilized to examine invasive capacity. The expression levels of E-cadherin and vimentin in BCa cells were measured using QRT-PCR. Western blot showed the EMT level to be the lowest in the niraparib+GD2 group. The transwell invasion assay suggested that the invasion ability of BCa cells was weakened in the niraparib+ GD2 group. CCK8 assay indicated that the proliferation ability of BCa cells was decreased. Scratch test suggested that the migration ability of BCa cells was weakened. PCR result showed that the niraparib + GD2 group had the most significant inhibitory effect on mRNA expression of EMT markers. Niraparib combined with a GD2-specific antibody exerted a more prominent inhibitory effect on BCa.

KRAS mutation promotes the colonization of Fusobacterium nucleatum in colorectal cancer by down-regulating SERTAD4.

This study explores and verifies potential molecular targets through which KRAS mutations regulate the colonization of Fusobacterium nucleatum (FN) in colorectal cancer (CRC). This study combined multiple bioinformatics methods and biological assays. Through The Cancer Genome Atlas, Gene Expression Omnibus, Human Protein Atlas, immunohistochemistry, and co-culture assays, we further confirmed the differential expression of SERTAD4 in CRC. We delved deeper into examining how expression of SERTAD4 is linked with immune cell infiltration and the enrichment of potential pathways. Lastly, through bacterial phenotypic assays, we validated the function of SERTAD4. As a molecule associated with KRAS mutations and FN infection, the expression levels of SERTAD4 were downregulated in CRC. The diagnostic efficacy of SERTAD4 for CRC is not inferior to that of CEA. Low expression of SERTAD4 is associated with poorer overall survival in CRC. Correlation analysis found that increased expression of SERTAD4 is associated with various immune cell infiltrations and immune checkpoint genes. Finally, bacterial adhesion and invasion assays verify that SERTAD4 inhibits the adhesion and invasion abilities of FN in CRC. This study demonstrates that SERTAD4 exerts a protective role in CRC by inhibiting the colonization of FN.

Detection of heat transfer mechanism in biological systems and HIF-1 α inducing invasion of liver cancer cells in hypoxic environments by activating STAT3

HIF-1α, as a hypoxia-inducing factor, can promote the invasion and metastasis of cancer cells by activating downstream signaling pathways. However, different heat transfer mechanisms in biological systems have important effects on the survival and function of tumor cells. The aim of this study was to investigate how the mechanisms of heat transfer in biological systems affect HIF-1α-mediated STAT3 activation and further induce the invasion ability of liver cancer cells in anoxic environment. The expression and activation of HIF-1α and STAT3 in hepatocellular carcinoma cell lines were detected by establishing anoxic model. At the same time, thermal imaging and heat transfer analysis methods were used to evaluate the heat transfer characteristics of cells under different temperature and hypoxia conditions. The effects of HIF-1α and STAT3 on invasion of hepatocellular carcinoma cells were analyzed in combination with cell migration and invasion experiments. The results showed that the expression of HIF-1α was significantly increased and the STAT3 signaling pathway was activated under hypoxia. The abnormal change of the heat transfer mechanism of biological system accelerates the invasion ability of hepatocellular carcinoma cells. Inhibition of HIF-1α expression can significantly reduce the activation level of STAT3, thereby inhibiting cell migration and invasion. This study reveals the interaction between the biological heat transfer mechanism and HIF-1α-STAT3 signaling pathway under hypoxia environment, which provides a new potential target for the treatment of malignant tumors such as liver cancer, and emphasizes the importance of regulating the heat transfer mechanism.

Histones Methyltransferase NSD3 Inhibits Lung Adenocarcinoma Glycolysis Through Interacting with PPP1CB to Decrease STAT3 Signaling Pathway.

Histones methyltransferase NSD3 targeting H3K36 is frequently disordered and mutant in various cancers, while the function of NSD3 during cancer initiation and progression remains unclear. In this study, it is proved that downregulated level of NSD3 is linked to clinical features and poor survival in lung adenocarcinoma. In vivo, NSD3 inhibited the proliferation, immigration, and invasion ability of lung adenocarcinoma. Meanwhile, NSD3 suppressed glycolysis by inhibiting HK2 translation, transcription, glucose uptake, and lactate production in lung adenocarcinoma. Mechanistically, as an intermediary, NSD3 binds to PPP1CB and p-STAT3 in protein levels, thus forming a trimer to dephosphorylate the level of p-STAT3 by PPP1CB, leading to the suppression of HK2 transcription. Interestingly, the phosphorylation function of PPP1CB is related to the concentration of carbon dioxide and pH value in the culture environment. Together, this study revealed the critical non-epigenetic role of NSD3 in the regulation of STAT3-dependent glycolysis, providing a piece of compelling evidence for targeting the NSD3/PPP1CB/p-STAT3 in lung adenocarcinoma.

Study on the expression of lncRNA PRKCA-AS1 in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most malignant tumors in the oral and maxillofacial region, with a poor prognosis. Previous studies have shown that long non-coding RNAs (lncRNAs) play a crucial role in tumor development by regulating the biological behavior of various cancer cells. The aim of this study is to explore the role and potential mechanisms of lncRNA PRKCA-AS1 in OSCC. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of lncRNA PRKCA-AS1 in OSCC tissues and cell lines. Cell proliferation, migration and invasion were conducted to assess the biological functions of OSCC cell lines. The expression of lncRNA PRKCA-AS1 in OSCC tissues was higher compared to that of adjacent non-cancerous tissues, and its expression level was associated with the depth of tumor infiltration, lymph node metastasis, and tumor node metastasis (TNM) staging. Compared to the control group of normal human oral keratinocytes (HOK), the expression of lncRNA PRKCA-AS1 was also elevated in OSCC cell lines. Knockdown of lncRNA PRKCA-AS1 significantly affected the proliferation, migration, and invasion ability of OSCC cells. However, when lncRNA PRKCA-AS1 was further overexpressed, changes in cell proliferation and migration ability did not show statistical differences. LncRNA PRKCA-AS1 is highly expressed in OSCC, and its expression level is positively correlated with the depth of tumor infiltration, lymph node metastasis, and TNM staging. LncRNA PRKCA-AS1 is involved in regulating the proliferation, migration, and invasion of OSCC cells.

ZYG11B participates in the modulation of colorectal cancer cell proliferation and immune infiltration and is a prognostic biomarker.

The biological function of ZYG11B is still unclear, and few studies on ZYG11B in colorectal cancer were reported. The purpose of our research is to detect the biological functions of ZYG11B in colorectal cancer through The Cancer Genome Atlas (TCGA) database online and the vitro cell experiments. The information of ZYG11B in colorectal cancer were downloaded from TCGA database. The bioinformatics analysis has been utilized to examine the expression, functional enrichment, association of immune, clinicopathological characteristics and diagnostic prognostic value. CCK-8 and apoptosis assays have been utilized to identify the abilities of progression and apoptosis. The abilities of invasion and migration were detected by transwell assay. In contrast to adjacent normal tissues, colorectal cancer tissues exhibited a notably diminished expression of ZYG11B (p < 0.001). Further examination through functional enrichment analysis unveiled the enrichment of various pathways associated with tumor proliferation and apoptosis. The implementation of CCK-8 and apoptosis assays validated the suppressive impact of ZYG11B on the progression of colorectal cancer cells (p < 0.001). A significant positive correlation was found between ZYG11B and Tcm and T helper cells (R ≥ 0.3, p < 0.001). Moreover, the expression of ZYG11B demonstrated a prominent presence among subjects without previous experience of colon polyps (p < 0.05), devoid of lymphatic infiltration (p < 0.01), and age ≤ 65 years (p < 0.01). Additionally, ZYG11B exhibited higher expression levels among patients diagnosed with colorectal adenocarcinoma (p < 0.05). Following the analysis of survival prognosis, it became evident that increased ZYG11B expression correlated with enhanced survival rates (p < 0.01) and the ability to accurately forecast the prognosis and survival of COAD/READ patients. ZYG11B plays a tumor suppressive role in the proliferation process of colorectal cancer and may have a broad application prospect in the diagnosis and prognosis evaluation of colorectal cancer with more study.

LncOCMRL1 promotes oral squamous cell carcinoma growth and metastasis via the RRM2/EMT pathway

BackgroundLong noncoding RNAs (lncRNAs) are widely involved in cancer development and progression, but the functions of most lncRNAs have not yet been elucidated. Metastasis is the main factor restricting the therapeutic outcomes of various cancer types, including oral squamous cell carcinoma (OSCC). Therefore, exploring the key lncRNAs that regulate OSCC metastasis and elucidating their molecular mechanisms will facilitate the development of new strategies for effective OSCC therapy.MethodsWe analyzed the lncRNA expression profiles of tumor tissues from OSCC patients with and without cervical lymph node metastasis, and OSCC cell lines. We revealed high expression of oral squamous cell carcinoma metastasis-related lncRNA 1 (lncOCMRL1) in OSCC patient tumor tissues with lymph node metastasis and highly metastatic OSCC cell lines. The effects of lncOCMRL1 knockdown on the invasion, migration and proliferation abilities of OSCC cells were explored through qRT-PCR, Transwell, colony formation, and cell proliferation experiments. The mechanism by which lncOCMRL1 promotes OSCC metastasis and proliferation was explored through RNA pull-down, silver staining, mass spectrometry, RIP, and WB experiments. To increase its translational potential, we developed a reduction-responsive nanodelivery system to deliver siRNA for antitumor therapy.ResultsWe determined that lncOCMRL1 is highly expressed in OSCC metastatic tumor tissues and cells. Functional studies have shown that high lncOCMRL1 expression can promote the growth and metastasis of OSCC cells both in vivo and in vitro. Mechanistically, lncOCMRL1 could induce epithelial-mesenchymal transition (EMT) via the suppression of RRM2 ubiquitination and thereby promote the proliferation, invasion, and migration of OSCC cells. We further constructed reduction-responsive nanoparticles (NPs) for the systemic delivery of siRNAs targeting lncOCMRL1 and demonstrated their high efficacy in silencing lncOCMRL1 expression in vivo and significantly inhibited OSCC tumor growth and metastasis.ConclusionsOur results suggest that lncOCMRL1 is a reliable target for blocking lymph node metastasis in OSCC.

Vaginal Mucosal Melanoma Cell Activation in Response to Photon or Carbon Ion Irradiation

PurposePrimary gynecological melanomas are uncommon with lower survival rates compared to cutaneous melanomas. Although melanocytes have been identified in a variety of mucosal membranes, little is known about their interactions or roles inside the mucosa layer. Melanin is a common pigment in nature and is endowed with several peculiar chemical, paramagnetic, and semiconductive characteristics. One of its latest explored functions is its interaction with ionizing radiation as a protective mechanism as well as its implication in the metastatic cascade of tumor cells. Materials and MethodsIn this work, we analyzed in vitro the effects of different doses of photon and carbon ion irradiation on dendrite formation, pigmentation, migration, and invasion abilities of human mucosal melanoma cells of the vagina. We evaluated the morphology and melanin production of HMV-II cells exposed to photon and carbon ion beams with single doses between 0.5 and 10 Gy. ResultsOur results showed that irradiation induces dendrite formation or elongation and pigmentation in HMV-II cells in a dose-type-dependent and radiation-type-dependent way but also a decrease in cell motility. ConclusionThe present study describes for the first time an induction of dendritic formation, melanin production, and alterations in migration and invasion abilities by low-linear energy transfer and high-linear energy transfer radiation in human mucosal melanoma cells, suggesting a radioprotective response to further possible exposures increasing the radioresistance of these cells.

A novel protein SPECC1-415aa encoded by N6-methyladenosine modified circSPECC1 regulates the sensitivity of glioblastoma to TMZ

BackgroundCircular RNAs (circRNAs) can influence a variety of biological functions and act as a significant role in the progression and recurrence of glioblastoma (GBM). However, few coding circRNAs have been discovered in cancer, and their role in GBM is still unknown. The aim of this study was to identify coding circRNAs and explore their potential roles in the progression and recurrence of GBM.MethodsCircSPECC1 was screened via circRNAs microarray of primary and recurrent GBM samples. To ascertain the characteristics and coding ability of circSPECC1, we conducted a number of experiments. Afterward, through in vivo and in vitro experiments, we investigated the biological functions of circSPECC1 and its encoded novel protein (SPECC1-415aa) in GBM, as well as their effects on TMZ sensitivity.ResultsBy analyzing primary and recurrent GBM samples via circRNAs microarray, circSPECC1 was found to be a downregulated circRNA with coding potential in recurrent GBM compared with primary GBM. CircSPECC1 suppressed the proliferation, migration, invasion, and colony formation abilities of GBM cells by encoding a new protein known as SPECC1-415aa. CircSPECC1 restored TMZ sensitivity in TMZ-resistant GBM cells by encoding the new protein SPECC1-415aa. The m6A reader protein IGF2BP1 can bind to circSPECC1 to promote its expression and stability. Mechanistically, SPECC1-415aa can bind to ANXA2 and competitively inhibit the binding of ANXA2 to EGFR, thus resulting in the inhibition of the phosphorylation of EGFR (Tyr845) and its downstream pathway protein AKT (Ser473). In vivo experiments showed that the overexpression of circSPECC1 could combine with TMZ to treat TMZ-resistant GBM, thereby restoring the sensitivity of TMZ-resistant GBM to TMZ.ConclusionsCircSPECC1 was downregulated in recurrent GBM compared with primary GBM. The m6A reader protein IGF2BP1 could promote the expression and stability of circSPECC1. The sequence of SPECC1-415aa, which is encoded by circSPECC1, can inhibit the binding of ANXA2 to EGFR by competitively binding to ANXA2 and inhibiting the phosphorylation of EGFR and AKT, thereby restoring the sensitivity of TMZ-resistant GBM cells to TMZ.