Identification and validation of Golgi apparatus-related signature for predicting prognosis and immunotherapy response in breast cancer.

BACKGROUND: The Golgi apparatus plays a pivotal role in various aspects of cancer. This study aims to investigate the predictive value of Golgi apparatus-related genes (GARGs) in breast cancer prognosis and immunotherapy response evaluation. METHODS: Transcriptional and clinical data from the TCGA-BRCA cohort and GSE96058 cohort were utilized to construct and validate a prognostic model for breast cancer using Cox regression analysis. Differences in immune landscape, somatic mutations, gene expression, drug sensitivity, and immunotherapy response between different risk groups were assessed. A prognostic nomogram for breast cancer was further developed and evaluated. qPCR and single-cell sequencing analyses were performed to validate the expression of GARGs. RESULTS: A total of 394 GARGs significantly associated with breast cancer prognosis were identified, leading to the construction of a prognostic risk feature comprising 10 GARGs. This feature effectively stratified breast cancer patients into high-risk and low-risk groups, with the high-risk group exhibiting significantly worse prognosis. Meanwhile, significant differences in clinicopathological features, immune infiltration, drug sensitivity, and immunotherapy response were observed between the high- and low-risk groups. The constructed nomogram incorporating these factors showed superior performance in prognostic assessment for breast cancer patients. Ultimately, the utilization of qPCR and single-cell sequencing techniques substantiated the disparate expression patterns of these prognostic genes in breast cancer. CONCLUSION: Our findings demonstrate that a prognostic risk feature derived from GARGs holds promising application potential for predicting prognosis and evaluating immunotherapy response in breast cancer patients.

Tunable Microwave Dielectric Properties in Rare-Earth Niobates via a High-Entropy Configuration Strategy To Induce Ferroelastic Phase Transition.

In this study, (La0.2Nd0.2Sm0.2Ho0.2Y0.2)(Nb1-xVx)O4 (0.1 ≤ x ≤ 0.4) ceramics were prepared using a high-entropy strategy via the solid-phase method. The crystal structure, microstructure, vibration modes, and phase transition were studied by X-ray diffraction, scanning electron microscopy/transmission electron microscopy (SEM/TEM), and Raman spectroscopy techniques. The phase of ceramics was confirmed to be a monoclinic fergusonite in the range of x ≤ 0.28, a tetragonal scheelite was in the range of 0.3 ≤ x ≤ 0.32, a complex phase of tetragonal scheelite, and zircon was observed in the ceramics when x ≥ 0.35. A zircon phase was also detected by TEM at x = 0.4. The ceramic at x = 0.25 exhibited outstanding temperature stabilization with εr = 18.06, Q × f = 56,300 GHz, and τf = -1.52 ppm/°C, while the x = 0.2 ceramic exhibited a low dielectric loss with εr = 18.14, Q × f = 65,200 GHz, and τf = -7.96 ppm/°C. Moreover, the permittivity, quality factor, and the temperature coefficient of resonance frequency were related to the polarizability, packing fraction, density, and the temperature coefficient of permittivity caused by phase transition. This is an effective method to regulate near-zero τf by the synergism of the high-entropy strategy and substituting Nb with V in LnNbO4 ceramics.

Hypoxia-inducible factor stabilisation-related lncRNAs in retinopathy of prematurity.

Long non-coding RNAs (lncRNAs) play an important role in the response to many diseases. The previous study reported the transcriptomes of mice that were cured of oxygen-induced retinopathy (OIR, retinopathy of prematurity (ROP) model) by hypoxia-inducible factor (HIF) stabilisation via HIF prolyl hydroxylase inhibition using the isoquinolone Roxadustat or the 2-oxoglutarateanalog dimethyloxalylglycine (DMOG). However, there is little understanding of how those genes are regulated. In the present study, 6918 known lncRNAs and 3654 novel lncRNAs were obtained, and a series of differentially expressed lncRNAs (DELncRNAs) were also identified. By cis- and trans-regulation analyses, the target genes of DELncRNAs were predicted. Functional analysis demonstrated that multiple genes were involved in the MAPK signalling pathway, adipocytokine signalling pathway was regulated by the DELncRNAs. By HIF-pathway analysis, two lncRNAs Gm12758 and Gm15283 were found that can regulate the HIF-pathway by targeting the Vegfa, Pgk1, Pfkl, Eno1, Eno1b and Aldoa genes. In conclusion, the present study provided a series of lncRNAs for further understanding and protecting the extremely premature infant from oxygen toxicity.

What is already known on this subject? Roxadustat can prevent oxygen-induced retinopathy (OIR) by two pathways: direct retinal hypoxia-inducible factor (HIF) stabilisation and induction of aerobic glycolysis or indirect hepatic HIF-1 stabilisation and increased serum angiokines. However, underlying the long non-coding RNAs (lncRNAs) that may regulate the HIF stabilisation-related genes have not been investigated thoroughly.What do the results of this study add? Six thousand nine hundred and eighteen known lncRNAs and 3654 novel lncRNAs were identified. GO and KEGG enrichment analysis showed that the MAPK signalling pathway and adipocytokine signalling pathway were regulated by the differentially expressed lncRNAs (DELncRNAs). Two lncRNAs Gm12758 and Gm15283 were found that may regulate the HIF-pathway by targeting the Vegfa, Pgk1, Pfkl, Eno1, Eno1b and Aldoa genes.What are the implications of these findings for clinical practice and/or further research? It provides a further rationale for protecting severe premature infants from oxygen poisoning.

Clinical Significance of TET2 in Female Cancers.

Female cancers refer to malignant tumors of the female reproductive system and breasts, which severely affect the physical and mental health of women. Although emerging experiment-based studies have indicated a potential correlation between ten-eleven translocation methylcytosine dioxygenase (TET2) and female cancers, no comprehensive studies have been conducted. Therefore, this study aimed to summarize the clinical value and underlying oncogenic functions of TET2 in female cancers, such as breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), ovarian serous cystadenocarcinoma (OV), uterine corpus endometrial carcinoma (UCEC), and uterine carcinosarcoma (UCS), based on the data obtained from The Cancer Genome Atlas. The expression of TET2 was decreased in most female cancers, and its high expression was distinctly associated with the favorable prognosis of most female cancers. Furthermore, CD8+ T-cell infiltration was not correlated with TET2 in OV, UCEC, and UCS, whereas tumor-associated fibroblast infiltration was significantly correlated with TET2 in BRCA, CESC, and OV. TET2 was co-expressed with the immune checkpoint molecules ADORA2A, CD160, CD200, CD200R1, CD44, CD80, NRP1 TNFSF4, and TNFSF15 in most female cancers. Enrichment analysis revealed that some signaling pathways involving TET2 and related genes were related to tumorigenesis. Immunohistochemical and immunofluorescence staining confirmed the results of cancer immune infiltration analysis in BRCA tissues. Therefore, this study provides evidence for the oncogenic functions and clinical value of TET2 in female cancers.

MiR-9-3p regulates the biological functions and drug resistance of gemcitabine-treated breast cancer cells and affects tumor growth through targeting MTDH.

This study explored the role of MTDH in regulating the sensitivity of breast cancer cell lines to gemcitabine (Gem) and the potential miRNAs targeting MTDH. The expression of MTDH in cancer tissues and cells was detected by immunohistochemical staining or qRT-PCR. The target genes for MTDH were predicted by bioinformatics and further confirmed by dual-luciferase reporter assay and qRT-PCR. Cancer cells were transfected with siMTDH, MTDH, miR-9-3p inhibitor, or mimics and treated by Gem, then CCK-8, colony formation assay, tube formation assay, flow cytometry, wound healing assay, and Transwell were performed to explore the effects of MTDH, miR-9-3p, and Gem on cancer cell growth, apoptosis, migration, and invasion. Expressions of VEGF, p53, cleaved caspase-3, MMP-2, MMP-9, E-Cadherin, N-Cadherin, and Vimentin were determined by Western blot. MTDH was high-expressed in cancer tissues and cells, and the cells with high-expressed MTDH were less sensitive to Gem, while silencing MTDH expression significantly promoted the effect of Gem on inducing apoptosis, inhibiting cell migration, invasion, and growth, and on regulating protein expressions of cancer cells. Moreover, miR-9-3p had a targeted binding relationship with MTDH, and overexpressed miR-9-3p greatly promoted the toxic effects of Gem on cancer cells and expressions of apoptosis-related proteins, whereas overexpressed MTDH partially reversed such effects of overexpressed miR-9-3p. The study proved that miR-9-3p regulates biological functions, drug resistance, and the growth of Gem-treated breast cancer cells through targeting MTDH.

Downregulation of long non-coding RNA MR4435-2HG suppresses breast cancer progression via the Wnt/ß-catenin signaling pathway.

Extensive research has contributed to the current understanding of the critical roles played by long non-coding RNAs in various types of cancer. The present study aimed to investigate the function and mechanism of the long non-coding RNA, MIR4435-2HG (also termed LINC00978), in breast cancer growth and metastasis. Using Gene Expression Profiling Interactive Analysis, an online web tool, it was revealed that MIR4435-2HG was upregulated in breast cancer tissue, and its high expression was associated with poor prognosis based on The Cancer Genome Atlas database. MIR4435-2HG knockdown increased cell apoptosis but decreased cell proliferation, migration and invasion. MIR4435-2HG knockdown increased pro-apoptotic protein expression but decreased anti-apoptotic protein expression. In addition, MIR4435-2HG knockdown leads to dysregulation of epithelial-to-mesenchymal transition-associated genes. Furthermore, knockdown of MIR4435-2HG results in inactivation of the Wnt/ß-catenin signaling pathway. The results of the present study demonstrate the tumor-promoting role of MIR4435-2HG in breast cancer progression.

LncRNA IGBP1-AS1/miR-24-1/ZIC3 loop regulates the proliferation and invasion ability in breast cancer.

BACKGROUND: Breast cancer (BC) is one of the malignant solid tumors with the highest morbidity in the world. Currently, the therapeutic outcome of different types of treatment can be unsatisfactory. Novel lncRNA biomarkers in BC remains to be further explored. METHODS: Different expression of lncRNAs among BC tissues and adjacent normal tissues were identified with microarray analyses. A series of in vivo and in vitro gain-of-function laboratory procedures were conducted to study the biological functions of IGBP1-AS1. The prognostic effects on IGBP1-AS1 survival were evaluated by using in situ hybridization and survival analysis. In addition, other experiments including RNA pull down analysis, RNA immunoprecipitation, luciferase reporter assays, and chromatin immunoprecipitation as well as validating assays conducted in vivo were applied to identify the target and regulatory mechanisms of IGBP1-AS1. RESULTS: Significant down-regulation of IGBP1-AS1 was discovered in the cell lines and tissues of BC. With respect to its biological function, overexpression of IGBP1-AS1 had inhibitory effects on the invasion and proliferation of BC cells in vivo as well as in vitro. Analysis of the samples obtained from BC patients indicated a positive effect of IGBP1-AS1 on survival outcomes. LncRNA IGBP1-AS1/miR-24-1/ZIC3 axis as a loop can regulate the proliferation and invasion of BC cells. CONCLUSIONS: IGBP1-AS1 could have inhibitory impact on the invasion and proliferation of BC and may serve as a promising biomarker for BC.

[Mesenchymal stem cells inhibit the expression of CD25 on phytohaemagglutinin-activated lymphocytes].

OBJECTIVE: To investigate the regulatory effects of rat mesenchymal stem cell (MSC) on T lymphocyte proliferation by examining the early activated markers such as CD25 and CD69. METHODS: MSC had been isolated and expanded in vitro. Then it was identified by cell morphology, membrane phenotype, and differentiation potential. Nylon wool column was applied to purify T-lymphocytes. MSCs and T-lymphocytes were cultured together and were stimulated by phytohaemagglutinin (PHA), and then the expressions of CD25 and CD69 were assessed. The levels of TGF-beta1 and IL-10 in the supernatants of MSC cultures were detected by using ELISA. RESULTS: (1) The expression of CD25 is suppressed in a dose-dependent manner when the T-lymphocytes are co-cultured with 10,000 MSCs or more, while 100 MSCs have no detectable effect; (2) The suppression of CD25 can be lasted more than 96 hrs; (3) The down regulation of CD25 is mediated by some soluble factors; (4) The reduced expression of CD25 caused by MSC inhibition is not mediated by TGF-beta1 and IL-10. CONCLUSION: MSCs have significant immune regulatory effects on PHA-stimulated T-lymphocyte culture. It might provide a remarkable immune suppression in organ-transplantation to achieve better outcome in the near future.

[Effects of vascular endothelial growth factor (VEGF) antisense oligodeoxynucleotide on mRNA and expression of VEGF, flt-1, and kinase insert domain containing receptor and VEGF excretion in human gallbladder carcinoma cells].

OBJECTIVE: To investigate the effects of vascular endothelial growth factor (VEGF) antisense oligodeoxynucleotide (ASODN) on the mRNA and protein expression of VEGF, Flt-1, and kinase insert domain containing receptor (KDR) and VEGF excretion in human gallbladder carcinoma cells. METHODS: Human gallbladder carcinoma cells of the line GBC-SD were cultured and transfected with VEGF ASODN and sense oligodeoxynucleotide (SODN) mediated by Oligofectamine. The toxicity of SODN and Oligofectamine to the GBC-SD cells was examined by MTT method. RT-PCR was used to detect the mRNA and expression of VEGF, Flt-1, and KDR, and ELISA was used to detect the protein expression of VEGF. RESULTS: MTT method showed that SODN and Oligofectamine were not toxic to the GBC-SD cells. The mRNA expression levels of VEGF, Flt-1, and KDR of the ASODN and ASODN + Oligofectamine groups were all significantly lower than those of the control group (all P < 0.05), and were the lowest 72 hours after transfection, and then gradually increased. ELISA showed that there were not significant differences in the VEGF protein concentration in the supernatant of the GBC-SD cells among the SODN, SODN + Oligofectamine, and control groups (all P < 0.05), however, the VEGF protein concentration in the supernatant of the GBC-SD cells of the ASDN and ASDN + Oligofectamine groups were significantly lower than that of the control group (both P < 0.05). CONCLUSION: VEGF ASODN inhibits the mRNA and protein expression of VEGF, Flt-1, and KDR and VEGF excretion in human gallbladder carcinoma cells. Oligofectamine strengthens the effect of ASODN.