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Abstract Breast cancer is common worldwide. Phosphoglycerate mutase 5 (PGAM5) belongs to the phosphoglycerate mutase family and plays an important role in many cancers. However, research on its role in breast cancer remains unclear. The present investigation highlights the significant expression of PGAM5 in breast cancer and its essential role in cell proliferation, invasion, apoptosis and the regulation of ferroptosis in breast cancer cells. Overexpression or knockdown of ubiquitin-specific protease 11 (USP11) promotes or inhibits the growth and metastasis of breast cancer cells, respectively, in vitro and in vivo. Mechanistically, USP11 stabilizes PGAM5 via de-ubiquitination, protecting it from proteasome-mediated degradation. In addition, the USP11/PGAM5 complex promotes breast cancer progression by activating iron death-related proteins, indicating that the synergy between USP11 and PGAM5 may serve as a predictor of disease outcome and provide a new treatment strategy for breast cancer.

BackgroundThyroid cancer (THCA) is the most prevalent malignant disease of the endocrine system, in which 5-year survival can attain about 95%, but patients with metastasis have a poor prognosis. Very little is known about the role of CAPN8 in the metastasis of THCA. In particular, the effect of CAPN8 on the tumor immune microenvironment (TIME) and immunotherapy response is unclear.Material and methodsMultiome datasets and multiple cohorts were acquired for analysis. Firstly, the expression and the prognostic value of CAPN8 were explored in public datasets and in vitro tumor tissues. Then, hierarchical clustering analysis was performed to identify the immune subtypes of THCA according to the expression of CAPN8 and the activities of related pathways. Subsequent analyses explored the different patterns of TIME, genetic alteration, DNA replication stress, drug sensitivity, and immunotherapy response among the three immune phenotypes. Finally, five individual cohorts of thyroid cancer were utilized to test the robustness and extrapolation of the three immune clusters.ResultsCAPN8 was found to be a significant risk factor for THCA with a markedly elevated level of mRNA and protein in tumor tissues. This potential oncogene could induce the activation of epithelial–mesenchymal transition and E2F-targeted pathways. Three subtypes were identified for THCA, including immune exhausted, inflamed, and immune desert phenotypes. The exhausted type was characterized by a markedly increased expression of inhibitory receptors and infiltration of immune cells but was much more likely to respond to immunotherapy. The immune desert type was resistant to common chemotherapeutics with extensive genomic mutation and copy number variance.ConclusionThe present study firstly explored the role of CAPN8 in the metastasis of THCA from the aspects of TIME. Three immune subtypes were identified with quite different patterns of prognosis, immunotherapy response, and drug sensitivity, providing novel insights for the treatment of THCA and helping understand the cross-talk between CAPN8 and tumor immune microenvironment.

Abstract Breast cancer is the most common cancer in women and its incidence rates are rapidly increasing in China. Understanding the molecular mechanisms of breast cancer tumorigenesis enables the development of novel therapeutic strategies. SEC61G is a subunit of the endoplasmic reticulum translocon that plays critical roles in various tumors. We aimed to investigate the expression and function of SEC61G in breast cancer. By analyzing The Cancer Genome Atlas breast cancer cohort, we found that SEC61G was highly expressed in breast cancer and predicted poor prognosis of breast cancer patients. Overexpression of SEC61G and its prognostic role was also confirmed in the Nanjing Medical University (NMU) breast cancer cohort. Functionally, we demonstrated that knockdown of SEC61G suppressed breast cancer cell proliferation, migration, invasion, and promoted breast cancer cell apoptosis in vitro. Xenograft breast tumor model revealed that knockdown of SEC61G inhibited breast tumor development in vivo. Furthermore, we demonstrated that SEC61G positively regulated glycolysis in breast cancer cells. Mechanistically, we showed that transcription factor E2F1 directly bound to the promoter of SEC61G and regulated its expression in breast cancer cells. SEC61G overexpression antagonized the effect of E2F1 knockdown in regulating breast cancer cell proliferation, invasion, and apoptosis. Finally, we demonstrated that the E2F1/SEC61G axis regulated glycolysis and chemo-sensitivity of Herceptin in breast cancer cells. Taken together, these results of in vitro and in vivo studies demonstrate that SEC61G promotes breast cancer development and metastasis via modulating glycolysis and is transcriptionally regulated by E2F1, which might be utilized as a promising therapeutic target of breast cancer treatment.

This study investigated the effects of gastrodin (GAS) on analgesic, anxiolytic, ferroptosis, and jejunal microbiota in chronic inflammatory pain mice. The chronic inflammatory pain model of C57BL/6J mice was established by hindpaw injection of complete Freund’s adjuvant (CFA). After GAS treatment, thermal hyperalgesia test, mechanical allodynia test, elevated plus-maze (EPMT), and open-field test (OFT) were performed to assess the behavioral changes of pain and anxiety. mRNAs of FTHI, GPX4, HO-1, and PTGS2 and jejunal microbiota were measured by qPCR. In CFA-injected C57BL/6 mice, we found that the mechanical and thermal pain threshold were increased with treatment of GAS. In EPMT, the number of entries in open arms and retention times of open arms were increased by GAS. In the OFT, the time spent in the central area was also increased. Furthermore, GAS enhanced mRNA expressions of FTHI, GPX4, and HO-1 but decreased the expression of PTGS2 in a dose-dependent manner. GAS is effective in the treatment of mice chronic inflammatory pain and anxiety-like behaviors. It may be exhibits potential neuroprotective effects through inhibition of ferroptosis independently of the intestinal microbiota.

BackgroundCD39 is one of the functional surface markers for T regulatory cells, the prognostic role and immune-related effects of CD39 in luminal breast cancer (BC) patients has not been evaluated yet. The aim of the current study was to explore the association between CD39 expression and clinic pathological characteristics and the prognosis in luminal BC patients.MethodsClinical information and RNA-sequencing (RNA-Seq) expression data were extracted from The Cancer Genome Atlas (TCGA). Patients were divided into a high or low CD39 expression group by the optimal cutoff value (4.18) identified from the receiver operating characteristic curve analysis. The relationships between CD39 expression and clinic pathological features were evaluated by the corresponding statistical tests. Survival analyses were applied to evaluate the overall survival between the high and low CD39 expression groups in luminal BC. Furthermore, Gene Expression Omnibus datasets were used for external data validation. Gene set enrichment analysis (GSEA) was also performed, and CIBERSORT was used to analyze the immune cell populations.ResultsAnalysis of 439 cases of tumor data showed that CD39 was overexpressed in luminal BC. The multivariable analysis suggested that CD39 expression was an independent prognostic factor for luminal BC patients. GSEA suggested that CD39 might play an important role in luminal BC progression through immune regulation. Analysis of immune cell patterns revealed high CD39 expression correlated to a higher proportion of CD8+ T cells and M2 macrophages.ConclusionThis study demonstrates that CD39 expression correlates with the prognosis of luminal BC through TCGA database mining. Further studies are warranted further to elucidate this potential novel therapeutic strategy for BC.

Abstract Background Cancer metastasis is the major reason for cancer related deaths, and the mechanism of cancer metastasis still unclear. RPLP1, a member of a group of proteins known as ribosomal proteins, is associated with tumorigenesis and primary cell immortalization and is involved in cellular transformation. However, the expression and potential function of RPLP1 in TNBC remain unclear. Methods The expression of RPLP1 in TNBC tissues and cell lines were detected with Real-Time PCR and western blotting. 81 cases of TNBC tissue samples and adjacent non-tumor tissue samples were tested by immunochemistry to determine the correlation between the RPLP1 expression and clinicopathological characteristics. In vitro, we determined the role and mechanistic pathways of RPLP1 in tumor metastasis in TNBC cell lines. Results In this study, we detected high levels of RPLP1 expression in TNBC samples and cell lines. RPLP1 is upregulated in triple-negative breast cancer (TNBC) tissues and cells, and high expression levels correlate with an increased risk of recurrence and metastasis. Furthermore, high RPLP1 expression was associated with a poor prognosis and was an independent prognostic marker for TNBC. In RPLP1-induced cancer metastasis, RPLP1 may increase cancer cell invasion, which is likely the result of its effect on the cancer cell epithelial-mesenchymal transition. Conclusions Altogether, our findings indicate RPLP1 is a poor prognostic potential biomarker and anti-metastasis candidate therapeutic target in triple-negative breast cancer.

Background/Aims: SUZ12 and EZH2 are two main components of polycomb repressive complex 2 (PRC2) that is known to be of great importance in tumorigenesis. EZH2 has been reported to play a vital role in pathogenesis of human cancer. However, whether SUZ12 has equivalent roles in tumorigenesis has not been demonstrated. Here, we investigated a possible role of SUZ12 for the proliferation of gastric cancer cells. Methods: Western-blot analysis was used to detected the levels of SUZ12, H3K27me3, EZH2 and p27 in ten gastric cell lines. SUZ12 was depleted by RNA interference. Cell cycle was detected by flow cytometry. Luciferase assays was to analyze whether miR-200b directly regulate SUZ12. Results: We found that SUZ12 depletion mediated by RNA interference (RNAi) led to a reduction of gastric cell numbers and arrested the cell cycle at G1/S point. As an important G1/S phase inhibitory gene, p27 is re-induced to some extent by SUZ12 knockdown. Furthermore, we demonstrated that SUZ12 was directly downregulated by miR-200b. Conclusion: We provide evidence suggesting that SUZ12 may be a potential therapeutic target for gastric cancer.

Various mechanical behaviors will happen at the same time when an engine operates. Based on this concept, in this paper, a systematical analysis method is presented to analyze the multiple mechanical behaviors (tribology, dynamics, stiffness, and strength) of the crankshaft-bearing system in an engine. By this method, the analyses of the tribology of bearing, the dynamics of crankshaft-bearing system and the dynamic stress of crankshaft can be accomplished simultaneously. For example, the effect of the journal misalignment of crankshaft and the elastic deformation of bearing bush on the dynamics of crankshaft-bearing system, the tribological performances of main bearings and the dynamic stress of crankshaft are analyzed emphatically. The results show that the journal misalignment of crankshaft and the elastic deformation of bearing bush have remarkable effect on the tribological performances of main bearings and the dynamic stress of crankshaft, but have little effect on the dynamics of crankshaft-bearing system. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small non-coding RNAs involved in an array of biological processes, and their dysregulation is associated with tumor development and progression. One such miRNA, miR-219-5p, is abnormally expressed in patients with colorectal cancer (CRC). In the present study, reverse transcription-quantitative polymerase chain reaction was performed to measure miR-219-5p expression in cells from both CRC tumors, and surrounding healthy tissue. MTT and invasion assays were used to determine the role of miR-219-5p in regulating CRC cell proliferation and invasion, respectively. A luciferase assay was then performed to assess the binding of miR-219-5p to the CAPS gene that encodes calcyphosin protein. The present study confirmed that miR-219-5p expression is significantly downregulated in CRC tissue. miR-219-5p knockdown promoted the growth of HCT-8 cells and increased the expression of calcyphosin protein (CAPS). On the other hand, overexpressing miR-219-5p inhibited HCT-8 cell growth and invasion, and downregulated CAPS expression. In addition, CAPS was identified as the functional downstream target of miR-219-5p by directly targeting its 3'-untranslated region. Therefore, miR-219-5p may function as a tumor suppressor by decreasing CAPS expression, and subsequently inhibit tumor proliferation and invasion. These results indicate that novel therapeutic strategies that increase miR-219-5p expression may be developed to treat CRC. [ABSTRACT FROM AUTHOR]

Bi2WO6 nanoplates were hydrothermally prepared and characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). The synthesized Bi2WO6 nanoplates were then used to fabricate modified carbon paste electrode (Bi2WO6-CPE) by a simple rubbing method. The result of electrochemical impedance spectroscopy indicated electron transfer resistance of the Bi2WO6-CPE was reduced vastly compared with CPE. In the meantime, cyclic voltammetry experiment demonstrated the Bi2WO6 nanoplates could accelerate the rate of electron transfer for the electrochemical reaction of diethylstilbestrol (DES) and bisphenol A (BPA) on the electrode. Moreover, the as-prepared electrode exhibited good selectivity toward simultaneous determination of DES and BPA with a rather low detection limit. By using differential pulse voltammetry (DPV) method, low detection limits of 15nM (S/N=3) and 20nM (S/N=3) for DES and BPA were obtained, with the linear calibration curves over the concentration range 50-2100nM and 70-1300nM, respectively. In addition, the proposed sensor was applied for the determination of analytes in spiked milk samples extracted from milk powder. [ABSTRACT FROM AUTHOR]