Colorectal cancer cannot be completely cured at present, and it is still an important clinical medical problem. TRAF6 is highly expressed in many malignant tumors. However, the role of TRAF6 in ...colorectal cancer is still controversial, mainly because the specific regulatory mechanism of colorectal cancer is still unclear, and the death mode of colorectal cancer cells has not been elucidated. The recent study found that TRAF6 inhibits necroptosis in colorectal cancer cells via the RIPK1/RIPK3/MLKL signaling pathway. The RIPK1 inhibitor Necrostain-1 inhibits colorectal cancer cell necroptosis via the RIPK1/RIPK3/MLKL signaling pathway. TRAF6 directly interacts with RIPK1 through the polyubiquitination of Lys48-linked RIPK1 and reduces the levels of RIPK1 protein in colorectal cancer cells, leading to necroptosis, thus promoting the proliferation of colorectal cancer cells. The recent study demonstrated that TRAF6 promotes colorectal cell progression by inhibiting the RIPK1/RIPK3/MLKL necroptosis signaling pathway, which may provide a new therapeutic target for colorectal cancer.
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic, inflammatory, and autoimmune disease, but its specific etiology and pathogenesis are still ...unclear. This study aimed to better discover the causative basement membrane (BM) genes of their subtypes and their associations.
The differential expression of BM genes between CD and UC was analyzed and validated by downloading relevant datasets from the GEO database. We divided the samples into 3 groups for comparative analysis. Construction of PPI networks, enrichment of differential gene functions, screening of Lasso regression models, validation of ROC curves, nomogram for disease prediction and other analytical methods were used. The immune cell infiltration was further explored by ssGSEA analysis, the immune correlates of hub BM genes were found, and finally, the hub central genes were screened by machine learning.
We obtained 6 candidate hub BM genes related to cellular immune infiltration in the CD and UC groups, respectively, and further screened the central hub genes ADAMTS17 and ADAMTS9 through machine learning. And in the ROC curve models, AUC > 0.7, indicating that this characteristic gene has a more accurate predictive effect on IBD. We also found that the pathogenicity-related BM genes of the CD and UC groups were mainly concentrated in the ADAMTS family (ADAMTS17 and ADAMTS9). Addition there are some differences between the two subtypes, and the central different hub BM genes are SPARC, POSTN, and ADAMTS2.
In the current study, we provided a nomogram model of CD and UC composed of BM genes, identified central hub genes, and clarified the similarities and differences between CD and UC. This will have potential value for preclinical, clinical, and translational guidance and differential research in IBD.
Colorectal cancer (CRC) is a formidable disease due to the intricate mechanisms that drive its proliferation and metastasis. Despite significant progress in cancer research, the integration of these ...mechanisms that influence cancer cell behavior remains elusive. Therefore, it is imperative to comprehensively elucidate the underlying mechanisms driving CRC proliferation and metastasis. In this study, we reported a novel role of SLC26A3 in suppressing CRC progression. We found that SLC26A3 expression was downregulated in CRC, which was proportionally correlated with survival. Our in vivo and in vitro experiments demonstrated that up-regulation of SLC26A3 inhibited CRC proliferation and metastasis, while down-regulation of SLC26A3 promoted CRC progression by modulating the expression level of IκB. Furthermore, we identified NHERF2 as a novel interacting protein of SLC26A3 responsible for stabilizing the IκB protein and removing ubiquitination modification. Mechanistically, SLC26A3 augmented the interaction between NHERF2 and IκB, subsequently reducing its degradation. This process inhibited the dissociation of p65 from the IκB/p65/p50 complex and reduced the translocation of p65 from the cytoplasm to the nucleus. Moreover, our investigation revealed that NF-κB/p65 directly bound to the promoter of SLC26A3, leading to a decline in its mRNA expression. Thus, SLC26A3 impeded the nuclear translocation of NF-κB/p65, enhancing the transcription of SLC26A3 and establishing a positive regulatory feedback loop in CRC cells. Collectively, these results suggest that a SLC26A3/NHERF2-IκB/NF-κB/p65 signaling loop suppresses proliferation and metastasis in CRC cells. These findings propose a novel SLC26A3-driven signaling loop that regulates proliferation and metastasis in CRC, providing promising therapeutic interventions and prognostic targets for the management of CRC.
To explore immune-related molecules that affect the prognosis of endometrial carcinoma (EC) using bioinformatic data mining. The expression data related to EC were downloaded from The Cancer Genome ...Atlas (TCGA) and Gene Expression Omnibus databases. After differential expression analysis, the intersection with immune related genes in the ImmPort database was used to obtain immune related differentially expressed genes (IRDEGs). The correlation between clinicopathological information and the prognosis of IRDEGs was further analyzed to obtain prognosis related differentially expressed immune genes (PRDEIG). Gene correlation analysis and Gene Set Enrichment Analysis (GSEA) enrichment analysis showed that PRDEIG was enriched in cancer-related functional pathways. We then analyzed the relationship between PRDEIG and immune cell infiltration, and further analyzed the mRNA and protein expression of PRDEIG in EC using TCGA and the human protein expression atlas (THPA) databases. After the intersection of the differential expression analysis results and immune-related genes, 4 IRDEGs were obtained: osteoglycin (OGN), LTBP4, CXCL12, and SPP1. After analyzing the relationship between 4 IRDEGs and clinicopathological parameters and prognosis of patients with EC, revealed that only OGN was not only related to tumor immunity, but also affected the prognosis of patients with EC. Gene correlation and GSEA enrichment of OGN were analyzed. The results showed that OGN was significantly enriched in 6 functional pathways: epithelial mesenchymal transition, KRAS signaling up, myogenesis, UV response, allograft rejection and apical junction. In addition, it was also found that OGN was significantly correlated with a variety of immune cells. The results of TCGA and THPA database showed that the mRNA and protein expression levels of OGN decreased in EC. OGN may affect the epithelial mesenchymal transformation (EMT) of tumor by affecting the infiltration of tumor immune cells.
Gastric cancer (GC) is a common malignant tumor of the digestive tract, and chemoresistance significantly impacts GC patients' prognosis. PANoptosis has been associated with oxaliplatin-induced cell ...death. However, the direct regulatory role of YBX1 in cellular chemoresistance through PANoptosis remains unclear. In this study, we investigated the impact of YBX1 on regulating PANoptosis and its influence on the resistance of gastric cancer cells to oxaliplatin. Through overexpression and silencing experiments, we assessed YBX1's effect on proliferation and PANoptosis regulation in gastric cancer cells. Additionally, we identified PPM1B and USP10 as interacting proteins with YBX1 and confirmed their influence on YBX1 molecular function and protein expression levels. Our results demonstrate that YBX1 suppresses PANoptosis, leading to enhanced resistance of gastric cancer cells to oxaliplatin. Furthermore, we found that PPM1B and USP10 play critical roles in regulating YBX1-mediated PANoptosis inhibition. PPM1B directly interacts with YBX1, causing dephosphorylation of YBX1 at serine 314 residue. This dephosphorylation process affects the deubiquitination of YBX1 mediated by USP10, resulting in decreased YBX1 protein expression levels and impacting PANoptosis and oxaliplatin resistance in gastric cancer cells. Additionally, we discovered that the 314th amino acid of YBX1 has a profound impact on its own protein expression abundance, thereby affecting the functionality of YBX1. In conclusion, our study reveals the significance of PPM1B-mediated dephosphorylation of YBX1 and USP10-mediated deubiquitination in regulating PANoptosis and sensitivity to oxaliplatin in gastric cancer cells. These findings offer a potential therapeutic strategy for patients with oxaliplatin-resistant gastric cancer.
•YBX1 inhibits PANoptosis and promotes oxaliplatin resistance in gastric cancer cells.•PPM1B interacts with YBX1 and dephosphorylates its serine residue at position 314.•The serine phosphorylation level of YBX1 at position 314 affects the ubiquitination level mediated by USP10.•PPM1B and USP10 jointly regulate YBX1 expression, thereby modulating PANoptosis and oxaliplatin resistance in GC.
Endometrial carcinoma (EC) is the most common gynecological cancer, but lacks specific targetable markers. In order to explore the immune-related molecules that affect the progression and prognosis ...of EC, we analyzed the differential expression of genes in different histological grades of the disease.
EC-related gene-expression data of different histological grades were downloaded from TCGA and GEO databases. The list of immune-related genes was obtained from the ImmPort database. In order to identity differentially-expressed genes (DEGs), differential-expression analysis was performed. The intersection of DEGs and immune-related genes was termed immune-related differentially-expressed genes (IRDEGs). IRDEGs were enriched in cancer-related functional pathways by gene-correlation analysis and GSEA-enrichment analysis. The association of IRDEGs with immune-cell tumor infiltration and gene polymorphisms was analyzed using IRDEG mRNA and protein-expression data in EC from TCGA and THPA databases.
Three IRDEGs, TNFSF15, SEMA3E and TNFSF10, were involved in the analysis of the prognosis of EC patients. IRDEGs were not only related to clinical characteristics but could also affect the prognosis of patients. Gene-correlation and GSEA-enrichment analysis of IRDEGs showed that TNFSF15 and TNFSF10 were co-enriched in the IL2-STAT5 functional pathway. IRDEGs had a significant correlation with a variety of immune-cell types infiltrating EC tumors and were related to EC prognosis. IRDEG mRNA- and protein-expression levels were increased in EC compared to normal tissues.
TNFSF15, SEMA3E and TNFSF10 may regulate the progression and prognosis of EC patients by affecting immune-cell infiltration of EC tumors.
Intersystem crossing (ISC) and reverse ISC (RISC) between singlet and triplet polaron-pairs (PP) and exciplex (EX) states, triplet-charge annihilation (TCA), and triplet–triplet annihilation (TTA) ...are well-known key spin-mixing processes in EX-based organic light-emitting diodes (EX-OLEDs) for improving the device optoelectronic performances. These microscopic processes usually show normal current dependencies; i.e., ISC and RISC weaken while TCA and TTA enhance with increasing bias current, respectively. Here, planar- and bulk-heterojunction EX-OLEDs (PHJ- and BHJ-EX-OLEDs) with good and poor hole-injection abilities were fabricated by modifying the device hole-injection layer. Amazingly, electroluminescence (EL) spectra are used to find that electron–hole coupling distances (r) of PP and EX states in PHJ-EX-OLEDs with good and poor hole-injection abilities are short and long, respectively. This unreported phenomenon only exists in PHJ-EX-OLEDs because holes and electrons separately accumulate on different sides of the donor/acceptor interface, and the distance from holes to the interface increases with decreasing hole-injection ability. However, r of PP and EX states in BHJ-EX-OLEDs are always short whether the devices have good or poor hole-injection abilities since holes and electrons are mixed together within the donor:acceptor blend layer. Furthermore, magneto-EL (MEL) traces of these devices are used as fingerprint detection techniques to distinguish various current-dependent ISC, RISC, TCA, and TTA processes of PP and EX states with short and long r. Specifically, current-dependent low-field effects (LFEs, B ≤ 10 mT) of MEL traces from PP and EX states with short r show the abnormal ISC process as the bias current increases (100 → 2000 μA), whereas those from PP and EX states with long r present rich conversions from normal ISC (100 → 400 μA) to abnormal RISC (600 → 1000 μA) and then to normal RISC (1000 → 1400 μA) and finally to abnormal ISC (1600 → 2000 μA) processes. These different current-dependent LFEs occur because PP and EX states with short and long r undergo monotonically and nonmonotonically current-dependent ISC and RISC processes, respectively. Moreover, current-dependent high-field effects (HFEs, 10 < B ≤ 300 mT) of MEL traces from EX states with a short r show the normal TCA process with increasing the bias current (100 → 2000 μA), but those from EX states with long r display an interesting conversion from abnormal TCA (100 → 1000 μA) to normal TTA (1000 → 2000 μA) processes. These different current-dependent HFEs happen because EX states with short and long r separately participate in the monotonically enhanced TCA process and the competition between the TCA and TTA processes. Obviously, this work enriches the physical understanding of the current-dependent ISC, RISC, TCA, and TTA processes of PP and EX states with short and long r in EX-OLEDs.
