Long-Term Outcomes of Selected Patients with IIIA-N2 Non-small Cell Lung Cancer Receiving Upfront Surgical Resection.

BACKGROUND: Stage IIIA non-small cell lung cancer (NSCLC) is a diverse group that requires multimodality treatment. The aim of this study was to report the long-term outcomes for patients with IIIA-N2 disease. METHODS: We conducted a retrospective review of cases with IIIA-N2 (T1-2N2) NSCLC who underwent upfront surgery. Kaplan-Meier curves and Cox proportional hazard analyses were used to assess the impact of various variables on survival. RESULTS: A total of 475 patients were ultimately included. With a median follow-up time of 108 months, the 5- and 10-year overall survival (OS) rates were 42.2% and 27.7%, respectively. R0 resection was found to be associated with improved progression-free survival (PFS) and OS compared with R1/R2 resection (p = 0.041 for PFS; p = 0.015 for OS). Patients with single-station N2 disease demonstrated significantly better PFS and OS than those with multiple-station N2 disease (p < 0.001 for PFS; p = 0.002 for OS). Following surgical resection, adjuvant therapy was significantly correlated with prolonged PFS and OS compared with those patients without any treatment. However, there was no significant difference in PFS and OS between chemotherapy and radiochemotherapy (p = 0.915 for PFS; p = 0.287 for OS). Patients with EGFR exon 19 deletion had significantly improved OS compared with those with L858R (p = 0.040). CONCLUSIONS: Our study shows promising long-term outcomes for selected patients with stage IIIA-N2 NSCLC treated with upfront surgery followed by adjuvant therapy, especially those with R0 resection and single-station N2. This study sheds light on the potential management and treatment options for this challenging population.

Distribution and concordance of PD-L1 expression by routine 22C3 assays in East-Asian patients with non-small cell lung cancer.

BACKGROUND: Currently, programmed death ligand-1 (PD-L1) expression has been widely applied in clinical trials and real-world clinical practice as a major biomarker for the efficacy of immune-checkpoint inhibitors. The purpose of this study is to reveal the distribution and concordance of PD-L1 expression in a large-scale consecutive cohort from East-Asian patients with non-small cell lung cancer (NSCLC). METHODS: PD-L1 testing was conducted using 22C3 assays, and cases were categorized into the high, low, and no expression of PD-L1 based on the tumor proportion score (TPS). Target-capture next-generation sequencing was used to identify molecular events. RESULTS: A total of 4550 patients and 4622 tests of PD-L1 expression were enrolled. There were 3017 (66.3%) patients with no PD-L1 expression (TPS < 1%), 1013 (22.3%) with low PD-L1 expression (TPS 1-49%), 520 (11.4%) with high PD-L1 expression (TPS ≥ 50%). Higher proportions of positive PD-L1 expression (TPS ≥ 1%) were observed in smokers, males, squamous cell carcinoma, and high-grade lung adenocarcinoma. Further analyses revealed fair agreement in primary and metastatic lesions (kappa = 0.533), poor agreement in multi-focal primary tumors (kappa = 0.045), and good agreement in biopsy and resection samples (kappa = 0.662) / two biopsy samples (kappa = 0.711). Mutational analyses revealed association between high PD-L1 expression (TPS ≥ 50%) and EGFR wild-type, KRAS mutation, ALK rearrangement, and TP53 mutation. CONCLUSION: The study reveals the unique distribution pattern of PD-L1 expression in a large-scale East-Asian cohort with NSCLC, the concordance of multiple PD-L1 tests, and the association between PD-L1 expression and molecular events. The results shed a light on the optimization of PD-L1 testing in clinical practice.

Rates of Bile Acid Diarrhoea After Cholecystectomy: A Multicentre Audit.

INTRODUCTION: Bile acid diarrhoea (BAD) can occur due to disruption to the enterohepatic circulation, e.g. following cholecystectomy. Post-cholecystectomy diarrhoea has been reported in 2.1-57.2% of patients; however, this is not necessarily due to BAD. The aim of this study was to determine the rates of bile acid diarrhoea diagnosis after cholecystectomy and to consider investigation practices. METHODS: A retrospective analysis of electronic databases from five large centres detailing patients who underwent laparoscopic cholecystectomy between 2013 and 2017 was cross-referenced with a list of patients who underwent 75SeHCAT testing. A 7-day retention time of <15% was deemed to be positive. Patient demographics and time from surgery to investigation were collected and compared for significance (p < 0.05). RESULTS: A total of 9439 patients underwent a laparoscopic cholecystectomy between 1 January 2013 and 31 December 2017 in the five centres. In total, 202 patients (2.1%) underwent investigation for diarrhoea via 75SeHCAT, of which 64 patients (31.6%) had a 75SeHCAT test result of >15%, while 62.8% of those investigated were diagnosed with bile acid diarrhoea (BAD). In total, 133 (65.8%) patients also underwent endoscopy and 74 (36.6%) patients had a CT scan. Median time from surgery to 75SeHCAT test was 672 days (SD ± 482 days). DISCUSSION/CONCLUSION: Only a small proportion of patients, post-cholecystectomy, were investigated for diarrhoea with significant time delay to diagnosis. The true prevalence of BAD after cholecystectomy may be much higher, and clinicians need to have an increased awareness of this condition due to its amenability to treatment. 75SeHCAT is a useful tool for diagnosis of bile acid diarrhoea.

Generation of a TAB2 knockout hESC line (WAe009-A-Z) derived from H9 using CRISPR/Cas9.

TGF-ß-activated kinase 1 binding protein 2 (TAB2) is an intermediate protein that connects TNFR1 and other receptor signals to the TGF-ß-activated kinase 1 (TAK1) signaling complex. TAB2 has been proved clinically relevant to congenital heart defects (CHD) and cardiomyopathy. In this study, we created a TAB2 knockout human embryonic stem cell line by CRISPR/Cas9 technology. The WAe009-A-Z cell line displayed stem cell morphology, pluripotency and normal karyotype, which could develop into three germ layers in vitro.

New dammarane-type triterpenoids from the whole plant of Euphorbia hypericifolia.

Euphorhypenoids A (1) and B (2), two new dammarane-type triterpenoids, along with four known tetracyclic triterpenoids (3-6), were isolated from the whole plant of Euphorbia hypericifolia. The structures of new compounds were mainly elucidated by a series of extensive spectroscopic methods, including HR-ESI-MS, NMR, IR, and UV. Compound 1 exhibited significant inhibitory effect on platelet aggregation at concentrations of 10 - 200 µM.

Causal associations between the gut microbiota and multiple myeloma: a two-sample Mendelian randomization study.

Background: Previous observational studies have indicated a potential association between the gut microbiota and multiple myeloma (MM). However, the relationship between the gut microbiota and MM remains unclear. This study aimed to ascertain the existence of a causal link between the gut microbiota and MM. Methods: To investigate the potential causal relationship between gut microbiota and MM, a two-sample Mendelian randomization (MR) analysis was conducted. Exposure data was obtained from the MiBioGen consortium, which provided genetic variants associated with 211 bacterial traits. MM outcome data was obtained from the FinnGen consortium. The selection of Single nucleotide polymorphisms estimates was performed through meta-analysis using inverse-variance weighting, and sensitivity analyses were conducted using weighted median, MR Egger, Simple mode, and MR-PRESSO. Results: The results of the study demonstrated a significant positive correlation between the genus Eubacterium ruminantium group and the risk of MM (OR 1.71, 95% CI 1.21 to 2.39). Conversely, the genus: Dorea (OR 0.46, 95% CI 0.24 to 0.86), Coprococcus1 (OR 0.47, 95% CI 0.22 to 1.00), RuminococcaceaeUCG014 (OR 0.57, 95% CI 0.33 to 0.99), Eubacterium rectale group (OR 0.37, 95% CI 0.18 to 0.77), and order: Victivallales (OR 0.62, 95% CI 0.41-0.94), class: Lentisphaeria (OR 0.62, 95% CI 0.41 to 0.94), exhibited a negative association with MM. The inverse variance weighting analysis provided additional support for these findings. Conclusion: This study represents an inaugural exploration of MR to investigate the connections between gut microbiota and MM, thereby suggesting potential significance for the prevention and treatment of MM.

Evolutionary proteogenomic landscape from pre-invasive to invasive lung adenocarcinoma.

Lung adenocarcinoma follows a stepwise progression from pre-invasive to invasive. However, there remains a knowledge gap regarding molecular events from pre-invasive to invasive. Here, we conduct a comprehensive proteogenomic analysis comprising whole-exon sequencing, RNA sequencing, and proteomic and phosphoproteomic profiling on 98 pre-invasive and 99 invasive lung adenocarcinomas. The deletion of chr4q12 contributes to the progression from pre-invasive to invasive adenocarcinoma by downregulating SPATA18, thus suppressing mitophagy and promoting cell invasion. Proteomics reveals diverse enriched pathways in normal lung tissues and pre-invasive and invasive adenocarcinoma. Proteomic analyses identify three proteomic subtypes, which represent different stages of tumor progression. We also illustrate the molecular characterization of four immune clusters, including endothelial cells, B cells, DCs, and immune depression subtype. In conclusion, this comprehensive proteogenomic study characterizes the molecular architecture and hallmarks from pre-invasive to invasive lung adenocarcinoma, guiding the way to a deeper understanding of the tumorigenesis and progression of this disease.

Enhanced gaseous acetone adsorption on montmorillonite by ball milling generated Si-OH and interlayer under synergistic modification with H2O2 and tetramethylammonium bromide.

Montmorillonite (Mt) is a potential adsorbent for volatile organic vapor removal from contaminated soils because of its rich reserves and porous nature, but its inertia surface property has limited its application for polar compounds. In this study, modifications of Mt were carried out by high energy ball milling with H2O2 and tetramethylammonium bromide (TMAB) to obtain adsorbents with both high porosity and abundant Si-OH groups (BHTMt). The microporous structure produced by TMAB insertion as well as the silanol (Si-OH) groups formed by H2O2 oxidation improved the adsorption of acetone by the modified material. The adsorption capacity of BHTMt for acetone was increased by 80% compared to the original Mt. The effect of H2O2 dosage on the adsorption performance for gaseous acetone was investigated by dynamic adsorption experiments. The adsorption kinetic results demonstrated that the adsorption of acetone by the modified material was subject to both physical and chemical adsorption. Density functional theory calculations indicated that there was no obvious interaction between TMAB and acetone, and the materials adsorbed acetone mainly through hydrogen bonding interaction of Si-OH as well as pore filling effects.

Prognostic effect of ground-glass opacity in subcentimeter invasive lung adenocarcinoma.

Background: Although subcentimeter nodules represent precursor or minimally invasive lung cancer in most cases, there are still a few that are subcentimeter invasive adenocarcinoma (IAC). The aim of this study was to investigate the prognostic effect of ground-glass opacity (GGO) and the optimal surgical procedure in this special group. Methods: Patients with subcentimeter IAC were enrolled and were categorized into pure GGO, part-solid, and solid nodules based on the radiological appearance. Cox proportional hazards model and the Kaplan-Meier method were used for survival analyses. Results: A total of 247 patients were enrolled. Among them, 66 (26.7%) were in the pure-GGO group, 107 (43.3%) were in the part-solid group, and 74 (30.0%) were in the solid group. Survival analysis demonstrated a significantly worse survival in the solid group. Cox multivariate analyses confirmed that the absence of GGO component was an independent risk factor for worse recurrence-free survival (RFS) and overall survival (OS). As for surgical procedures, lobectomy did not provide a significant better RFS or OS than sublobar resection in the whole cohort or in a subgroup of patients with solid nodules. Conclusions: The radiological appearance stratified the prognosis of IAC with size of smaller than or equal to 1 cm. Sublobar resection may be feasible for subcentimeter IAC, even for those appearing as solid nodules; however, caution should be taken when applying wedge resection.

Mechanistic insights into ball milling enhanced montmorillonite modification with tetramethylammonium for adsorption of gaseous toluene.

Montmorillonite is widely used for pollutants adsorption due to its porous structure and low price. However, the low specific surface area and small porosity limit its application in gas adsorption field. In this study, montmorillonite was organically modified using a facile dry ball milling method by tetramethylammonium bromide. The adsorption behaviour of toluene as a model VOC compound on organic montmorillonite was systematically investigated through adsorption breakthrough curves, adsorption kinetics and isotherms. After modification by ball milling, the specific surface area of ball milling with tetramethylammonium bromide for montmorillonite modification (BMTMt) was increased from 20.6 m2/g to 186.4 m2/g, and the microporosity proportion was up to 47%. Dynamic adsorption experiments showed that the best performance of BMTMt for toluene (55.9 mg/g) was 6 times higher than that of original montmorillonite (8.8 mg/g). Compared with the water bath preparation method, ball milling method promoted the intercalation of tetramethylammonium bromide into the layers of montmorillonite, resulting in a higher proportion of micropores. Density functional theory calculations indicated that the interaction between tetramethylammonium bromide and montmorillonite was mainly electrostatic forces, and the enhanced adsorption performance for toluene was mainly through microporous filling. BMTMt was proved to be a promising adsorbent for VOCs removal.

Therapeutic application of chick early amniotic fluid: effective rescue of acute myocardial ischemic injury by intravenous administration.

Myocardial regeneration has been considered a promising option for the treatment of adult myocardial injuries. Previously, a chick early amniotic fluid (ceAF) preparation was shown to contain growth-related factors that promoted embryonic growth and cellular proliferation, though the nature of the components within ceAF were not fully defined. Here we tested whether this ceAF preparation is similarly effective in the promotion of myocardial regeneration, which could provide an alternative therapeutic for intervening myocardial injury. In this study, a myocardial ischemic injury model was established in adult mice and pigs by multiple research entities, and we were able to show that ceAF can efficiently rescue damaged cardiac tissues and markedly improve cardiac function in both experimental models through intravenous administration. ceAF administration increased cell proliferation and improved angiogenesis, likely via down-regulation of Hippo-YAP signaling. Our data suggest that ceAF administration can effectively rescue ischemic heart injury, providing the key functional information for the further development of ceAF for use in attenuating myocardial injury.

Activation of Pancreatic Acinar FXR Protects against Pancreatitis via Osgin1-Mediated Restoration of Efficient Autophagy.

Pancreatitis is the leading cause of hospitalization in gastroenterology, and no medications are available for treating this disease in current clinical practice. FXR plays an anti-inflammatory role in diverse inflammatory diseases, while its function in pancreatitis remains unknown. In this study, we initially observed a marked increase of nuclear FXR in pancreatic tissues of human patients with pancreatitis. Deleting the FXR in pancreatic acinar cells (FXRacinarΔ/Δ ) led to more severe pancreatitis in mouse models of caerulein-induced acute and chronic pancreatitis, while the FXR agonist GW4064 significantly attenuated pancreatitis in caerulein or arginine-induced acute pancreatitis and caerulein-induced chronic pancreatitis. FXR deletion impaired the viability and stress responses of pancreatic exocrine organoids (PEOs) in vitro. Utilizing RNA-seq and ChIP-seq of PEOs, we identified Osgin1 as a direct target of FXR in the exocrine pancreas, which was also increasingly expressed in human pancreatitis tissues compared to normal pancreatic tissues. Pancreatic knockdown of Osgin1 by AAV-pan abolished the therapeutic effects of FXR activation on pancreatitis, whereas pancreatic overexpression of Osgin1 effectively alleviated caerulein-induced pancreatitis. Mechanistically, we found that the FXR-OSGIN1 axis stimulated autophagic flux in the pancreatic tissues and cell lines, which was considered as the intrinsic mechanisms through which FXR-OSGIN1 protecting against pancreatitis. Our results highlight the protective role of the FXR-OSGIN1 axis in pancreatitis and provided a new target for the treatment of this disease.

ß-hydroxybutyrate inhibits ferroptosis-mediated pancreatic damage in acute liver failure through the increase of H3K9bhb.

Acute pancreatitis and hyperamylasemia are often seen in patients with acute liver failure (ALF). However, the underlying mechanisms remain elusive. This study describes pancreatic tissue damage and exocrine dysfunction in a mouse model of major-liver-resection-induced ALF. The analysis of 1,264 clinical cases of liver failure (LF) showed that the incidence of hyperamylasemia and hyperlipasemia in patients with LF is 5.5% and 20%, respectively. Metabolomic studies indicate that glutathione (GSH)-deficiency-caused ferroptosis contributes to pancreatic damage in mouse ALF. ß-hydroxybutyrate (ß-HB) is the only metabolite downregulated in the liver, serum, and pancreas. Our data suggest that ß-HB protects pancreatic cells and tissues from GSH-deficiency-caused ferroptosis. ß-HB administration in ALF mice restores the expression of ferroptosis-suppressor genes through histone H3 lysine 9 ß-hydroxybutyrylation (H3K9bhb)-mediated chromatin opening. Our findings highlight ß-HB as an endogenous metabolite regulating ferroptosis in the pancreas and extend our understanding of the pathophysiology of ALF-induced pancreatitis.

Prototype readout electronics of a double-sided silicon strip detector for space exploration.

Double-sided silicon strip detectors (DSSDs) have been widely used in interplanetary exploration. In this study, the prototype readout electronics of a DSSD for space exploration is presented. It mainly includes a front-end readout module (FEM) and a data acquisition module (DAM). The FEM is responsible for acquiring the charge of the DSSD signals based on an application-specific integrated circuit and polarity inverter circuits. The DAM with a field programmable gate array is employed to perform online calculations of the position and energy as well as data packaging and transfer. Test results show that the electronics has dynamic ranges of 6-2500 and -6 to -2500 fC with an integral nonlinearity of no more than 0.5%, while the root-mean-square noise level is less than 1.9 fC. Joint tests with the DSSD indicate that a full width at half maximum energy resolution of 3.25% at 5.486 MeV and a position resolution of 1.19 mm were achieved.

Effect of Different Dosage Frequency of Polymyxin B on Rat Nephrotoxicity.

BACKGROUND: Polymyxin B, as the final treatment against multidrug-resistant Gram-negative bacilli, is widely used in clinical practice. However, little is known about the nephrotoxicity of polymyxin B. The purpose of this study was to elucidate the relationship between polymyxin B nephrotoxicity and daily administration frequency. METHODS: Sprague-Dawley rats were randomly divided into three groups: 18 mg/kg/q24 h group (Group A, once daily), 9 mg/kg/q12 h group (Group B, twice daily), and normal saline control group (Group C). The rats were injected subcutaneously for 5 consecutive days with the same daily total dose and different frequency of administration. The serum creatinine (SCr) and blood urea nitrogen (BUN) of each group before administration (0 h), and 8 and 24 h after administration, were measured by tail vein blood sampling. On the sixth day, the rats in each group were killed, the left kidney was taken for pathological section observation, and the results of each group were compared. RESULTS: After 96 h of administrated polymyxin B, the total average level of SCr in Group A was 56.98±12.42 µmol/L, that of Group B was 52.02±8.68 µmol/L, and that of Group C was 34.36±5.39 µmol/L. BUN was 9.86±4.58, 10.54±4.08, and 3.55±0.73 mmol/L in Groups A, B, and C, respectively. The daily urinary protein excretion was 5004.45±1333.84 µg in Group A, 4608.04±1444.42 µg in Group B, and 2096.33±215.28 µg in Group C. In addition, according to the observation of pathological slices, compared with Group A, the number of exfoliated and necrotic cells of renal tubules in Group B was higher, and the morphological changes were more serious. CONCLUSION: The experimental results showed that the renal toxicity in rats treated with a twice-daily subcutaneous dose of polymyxin B was higher than that in rats treated with once-daily dose of polymyxin B.

Potential Crosstalk between Liver and Extra-liver Organs in Mouse Models of Acute Liver Injury.

Carbon tetrachloride (CCl4), Concanavalin A (ConA), bile duct ligation (BDL), and liver resection (LR) are four types of commonly used mouse models of acute liver injury. However, these four models belong to different types of liver cell damage while their application situations are often confounded. In addition, the systematic changes of multiple extra-liver organs after acute liver injury and the crosstalk between liver and extra-liver organs remain unclear. Here, we aim to map the morphological, metabolomic and transcriptomic changes systematically after acute liver injury and search for the potential crosstalk between the liver and the extra-liver organs. Significant changes of transcriptome were observed in multiple extra-liver organs after different types of acute liver injury despite dramatic morphological damage only occurred in lung tissues of the ConA/BDL models and spleen tissues in the ConA model. Liver transcriptomic changes initiated the serum metabolomic alterations which correlated to transcriptomic variation in lung, kidney, and brain tissues of BDL and LR models. The potential crosstalk might lead to pulmonary damage and development of hepatorenal syndrome (HRS) and hepatic encephalopathy (HE) during liver injury. Serum derived from acute liver injury mice damaged alveolar epithelial cells and human podocytes in vitro. Our data indicated that different types of acute liver injury led to different transcriptomic changes within extra-liver organs. Integration of serum metabolomics and transcriptomics from multiple tissues can improve our understanding of acute liver injury and its effect on the other organs.

MicroRNA-3648 Is Upregulated to Suppress TCF21, Resulting in Promotion of Invasion and Metastasis of Human Bladder Cancer.

Although microRNAs (miRNAs) are well-known for their potential in cancer, the function and mechanisms of miR-3648 have barely been explored in any type of cancer. We show here that miR-3648 is upregulated in human BC tissues in comparison with adjacent non-tumor tissues. Functional studies showed that inhibition of miR-3648 expression in the human invasive BC UMUC3 and T24T cell lines decreased migration and invasion in vitro and suppressed lung metastasis in vivo, whereas miR-3648 overexpression promoted BC cell migration and invasion. A bioinformatics screen and mRNA 3' UTR luciferase reporter assay showed that transcription factor 21 (TCF21) was a direct target of miR-3648, and the results obtained from using a miR-3648 inhibitor revealed that miR-3648 inhibited TCF21 protein expression by reduction of its mRNA stability. Further, Kisspeptin 1 (KISS1) was identified as a TCF21 downstream effector responsible for miR-3648-mediated BC invasion and lung metastasis. Collectively, the present results suggest that miR-3648 is overexpressed and plays an oncogenic role in mediation of BC invasion and metastasis through directing the TCF21/KISS1 axis, revealing miR-3648 as a potential biomarker for BC prognosis and a target for BC therapy.

MicroRNA-411 Downregulation Enhances Tumor Growth by Upregulating MLLT11 Expression in Human Bladder Cancer.

Although several previous studies have reported the implication of various microRNAs (miRNAs) in regulation of human bladder cancer (BC) development, alterations and function of many miRNAs in bladder cancer growth are not explored yet at present. Here, we screened 1,900 known miRNAs and first discovered that miR-411 was one of the major miRNAs, which was down-regulated in n-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced BCs. This miR-411 down-regulation was also observed in human BC tissues and cell lines. The results from evaluating the relationship between miR-411 and patient survival in BC using the TCGA (The Cancer Genome Atlas) database indicated that miR-411 was positively correlated with DFS (disease-free survival). Our studies also showed that miR-411 inhibited tumor growth of human BC cells in a xenograft animal model. Mechanistic studies revealed that overexpression of miR-411 repressed the expression of ALL1-fused gene from the chromosome 1q (AF1q) (MLLT11) by binding to the 3' untranslated region (UTR) of mllt11 mRNA and in turn induced p21 expression and caused cell cycle arrest at the G2/M phase, further inhibiting BC tumor growth. Collectively, our results improve our understanding of the role of miR-411 in BC tumor growth and suggest miR-411 and MLLT11 as potential new targets for the treatment of BC patients.

NF-κB p65 Overexpression Promotes Bladder Cancer Cell Migration via FBW7-Mediated Degradation of RhoGDIα Protein.

BACKGROUND: Since invasive bladder cancer (BC) is one of the most lethal urological malignant tumors worldwide, understanding the molecular mechanisms that trigger the migration, invasion, and metastasis of BC has great significance in reducing the mortality of this disease. Although RelA/p65, a member of the NF-kappa B transcription factor family, has been reported to be upregulated in human BCs, its regulation of BC motility and mechanisms have not been explored yet. METHODS: NF-κBp65 expression was evaluated in N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced high invasive BCs by immunohistochemistry staining and in human BC cell lines demonstrated by Western Blot. The effects of NF-κBp65 knockdown on BC cell migration and invasion, as well as its regulated RhoGDIα and FBW7, were also evaluated in T24T cells by using loss- and gain-function approaches. Moreover, the interaction of FBW7 with RhoGDIα was determined with immunoprecipitation assay, while critical role of ubiquitination of RhoGDIα by FBW7 was also demonstrated in the studies. RESULTS: p65 protein was remarkably upregulated in the BBN-induced high invasive BCs and in human BC cell lines. We also observed that p65 overexpression promoted BC cell migration by inhibiting RhoGDIα expression. The regulatory effect of p65 on RhoGDIα expression is mediated by its upregulation of FBW7, which specifically interacted with RhoGDIα and promoted RhoGDIα ubiquitination and degradation. Mechanistic studies revealed that p65 stabilizing the E3 ligase FBW7 protein was mediated by its attenuating pten mRNA transcription. CONCLUSIONS: We demonstrate that p65 overexpression inhibits pten mRNA transcription, which stabilizes the protein expression of ubiquitin E3 ligase FBW7, in turn increasing the ubiquitination and degradation of RhoGDIα protein and finally promoting human BC migration. The novel identification of p65/PTEN/FBW7/RhoGDIα axis provides a significant insight into understanding the nature of BC migration, further offering a new theoretical support for cancer therapy.