Background:Ubiquitin-conjugating enzyme E2C (UBE2C) has been shown to be associated with the occurrence of various cancers and involved in many tumorigenic processes. This study aimed to investigate the specific molecular mechanism through which UBE2C affects breast cancer (BC) proliferation.Methods:BC-related datasets were screened according to filter criteria in the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. Then differentially expressed genes (DEGs) were identified using Venn diagram analysis. By using DEGs, we conducted the following analyses including Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI), and survival analysis, and then validated the function of the hub gene UBE2C using quantitative reverse transcription-polymerase chain reaction (RT-qPCR), cell counting kit-8 (CCK-8) assay, transwell assay, and Western blot assay.Results:In total, 151 DEGs were identified from the GEO and TCGA databases. The results of GO analysis demonstrated that the DEGs were significantly enriched with mitotic nuclear division, lipid droplet, and organic acid-binding. KEGG analysis showed that the peroxisome proliferators-activated receptor (PPAR) signaling pathway, regulation of lipolysis in adipocytes, and proximal tubule bicarbonate reclamation were significantly enriched in the signal transduction pathway category. The top three hub genes that resulted from the PPI network were FOXM1, UBE2C, and CDKN3. The results of survival analysis showed a close relationship between UBE2C and BC. The results of CCK-8 and transwell assays suggested that the proliferation and invasion of UBE2C knockdown cells were significantly inhibited (P < 0.050). The results of Western blot assay showed that the level of phosphorylated phosphatase and tensin homology deleted on chromosome 10 (p-PTEN) was obviously increased (P < 0.050), whereas the levels of phosphorylated protein kinase B (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), and hypoxia-inducible factor-1 alpha (HIF-1α) were dramatically decreased (P < 0.050) in the UBE2C knockdown cell.Conclusion:UBE2C can promote BC proliferation by activating the AKT/mTOR signaling pathway.
Background: Breast cancer is one of the most common cancer in women and a proportion of patients experiences brain metastases with poor prognosis. The study aimed to construct a novel predictive clinical model to evaluate the overall survival (OS) of patients with postoperative brain metastasis of breast cancer (BCBM) and validate its effectiveness. Methods: From 2010 to 2020, a total of 310 female patients with BCBM were diagnosed in The Affiliated Cancer Hospital of Xinjiang Medical University, and they were randomly assigned to the training cohort and the validation cohort. Data of another 173 BCBM patients were collected from the Surveillance, Epidemiology, and End Results Program (SEER) database as an external validation cohort. In the training cohort, the least absolute shrinkage and selection operator (LASSO) Cox regression model was used to determine the fundamental clinical predictive indicators and the nomogram was constructed to predict OS. The model capability was assessed using receiver operating characteristic, C-index, and calibration curves. Kaplan–Meier survival analysis was performed to evaluate clinical effectiveness of the risk stratification system in the model. The accuracy and prediction capability of the model were verified using the validation and SEER cohorts. Results: LASSO Cox regression analysis revealed that lymph node metastasis, molecular subtype, tumor size, chemotherapy, radiotherapy, and lung metastasis were statistically significantly correlated with BCBM. The C-indexes of the survival nomogram in the training, validation, and SEER cohorts were 0.714, 0.710, and 0.670, respectively, which showed good prediction capability. The calibration curves demonstrated that the nomogram had great forecast precision, and a dynamic diagram was drawn to increase the maneuverability of the results. The Risk Stratification System showed that the OS of low-risk patients was considerably better than that of high-risk patients (P < 0.001). Conclusion: The nomogram prediction model constructed in this study has a good predictive value, which can effectively evaluate the survival rate of patients with postoperative BCBM.
LINC00461 represents a new long noncoding RNA. However, it is unclear whether LINC00461 is associated with glucose metabolism and proliferation in triple-negative breast cancer. Here, we show that LINC00461 overexpression induces glucose metabolism and proliferation in TNBC, whereas its downregulation markedly reduces glucose metabolism and proliferation. Mechanistically, LINC00461 might function in TNBC by binding with HSP90. Then, it enhances the interaction between HSP90 and c-Myc and inhibits ubiquitination and degradation of c-Myc to regulate c-Myc target genes-LDHA. Clinically, LINC00461 has tight associations with tumor grade and TNM in cancer patients. There is compelling evidence LINC00461 may be exploited as a possible novel molecular marker and therapeutic target in TNBC.
Objective. To evaluate the diagnostic value of the nanometer carbon suspension tracer staining technique in sentinel lymph node biopsy of breast cancer is the objective of this study. Methods. The PubMed, Embase, Cochrane Library (Central), and Web of Science (SCI Expanded), and Chinese databases (CNKI, VIP, Wan Fang, and CBM) were systematically searched for studies on the diagnostic value of nanocarbon suspension in sentinel lymph node biopsy of breast cancer. Two reviewers independently assessed the methodological quality of each study using the QUADAS-2 tool. The extracted valid data were calculated using Meta-Disc1.4 software and tested for heterogeneity. STATA14.0 software was selected for sensitivity analysis of the included studies, and publication bias was assessed using Deeks’ forest plot asymmetry test. Results. A total of 10 studies were obtained. The pooled data were as follows: sensitivity, 0.92 (0.88~0.95); specificity, 0.99 (0.98~1.00); positive likelihood ratio, 69.24 (30.34~158.02); negative likelihood ratio, 0.09 (0.06~0.13); and the combined diagnostic odds ratio, 747.40 (285.77~1954.76), AUC = 0.9881 . Nanocarbon suspension tracers have an accuracy rate of 98.81% in the diagnosis of sentinel lymph nodes in breast cancer. Conclusion. Tracer staining technology based on nanocarbon suspension can accurately assess the status of lymph nodes in sentinel lymph node biopsy of breast cancer and has good stability and operability, which is worthy of clinical promotion.
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